Podcasts about cd38

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Best podcasts about cd38

Latest podcast episodes about cd38

NutritionFacts.org Video Podcast
The Third Way to Boost NAD+

NutritionFacts.org Video Podcast

Play Episode Listen Later Apr 21, 2025 7:01


How can we conserve NAD+ by preventing overactivation of the enzymes PARP-1 and CD38, which guzzle NAD+?

Everyday Wellness
BONUS: Why NAD Matters for Women's Health & Hormones with Dr. Andrew Salzman

Everyday Wellness

Play Episode Listen Later Apr 14, 2025 68:26


This podcast is the first episode in a series featuring companies I am eager to explore and share with my community. Today, I am thrilled to welcome Dr. Andrew Salzman, a Harvard-trained medical doctor, pioneering scientist, and esteemed inventor. Dr. Salzman is the Chief Medical Officer at Wonderfeel, where he applies over three decades of medical innovation. His research into DNA repair with NAD-activated enzymes led the way for a groundbreaking treatment for BRCA-related breast and ovarian cancers, which he licensed to Genentech. Dr. Salzman was among the first researchers to publish papers on the gut microbiome and leaky gut syndrome in the 1980s, and he has published over 170 peer-reviewed papers and holds more than 50 patents. In our conversation today, we dive into what NAD is, its significance, why it matters, and how it impacts fertility, menopause, and sexual health. Dr. Salzman walks us through the symptoms of NAD deficiency and explains how an enzyme called CD38 can emerge when NAD levels are low, triggering inflammation and oxidative stress. We explore the difference between pharmaceutical agents and nutraceuticals, examining why oral NMN is preferable and how sleep and alcohol can influence NAD levels. We cover the risk factors for breast, ovarian, and uterine cancers, looking at what we can do to reduce them, and we also talk about Wonderfeel and how their supplements and botanicals enhance wellness for women.  This is an invaluable discussion with Dr. Salzman, so you will likely want to listen to it more than once. IN THIS EPISODE YOU WILL LEARN: How our NAD levels change as we get older The role of NAD in energy production  How oxidative stress and inflammation affect NAD levels in the ovaries Why NAD is essential for sexual health Lifestyle choices that could affect NAD levels How inflammation can increase CD 38 levels and deplete NAD Why oral administration of NMN or NR is the most practical and effective method for maintaining NAD levels How alcohol affects NAD levels and increases the risk of cancer How, with Dr. Salzman's input, Wonderfeel developed a product combining NMN with botanicals to enhance NAD levels Connect with Cynthia Thurlow   Follow on Twitter Instagram LinkedIn Check out Cynthia's website Submit your questions to support@cynthiathurlow.com Connect with Dr. Andrew Salzman On the Wonderfeel website .

Oncotarget
Single Protein Mimics Retinoic Acid Therapy to Help Leukemia Cells Mature

Oncotarget

Play Episode Listen Later Mar 26, 2025 3:51


BUFFALO, NY - March 31, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on March 21, 2025, titled “FGR Src family kinase causes signaling and phenotypic shift mimicking retinoic acid-induced differentiation of leukemic cells." A research team led by first author Noor Kazim and corresponding author Andrew Yen from Cornell University discovered that the FGR protein—traditionally considered a cancer-promoting molecule—can instead trigger leukemia cells to mature. This effect mirrors the response usually induced by retinoic acid (RA); a compound derived from vitamin A that is widely used in cancer therapy. Their finding presents a potential new path for therapies targeting acute myeloid leukemia (AML) and related cancers. Acute myeloid leukemia is often treated using RA-based therapies that force immature white blood cells to mature, slowing their rapid growth. Retinoic acid works through complex signaling and gene regulation involving a group of proteins that orchestrate this transformation. In this study, the team used HL-60 cells, a model for human leukemia, and engineered them to express FGR. Surprisingly, the presence of FGR alone was enough to make these cells mature in a way almost identical to what happens with RA treatment. They began producing well-known markers of maturation such as CD38 and CD11b, generated reactive oxygen species (ROS), and expressed the inhibitor of the cell cycle, p27, all signs that the cells had shifted from a cancer-like, fast-dividing state to a more specialized, mature form. Further analysis revealed that FGR activated a group of proteins known as the "signalsome," which helps trigger the changes needed for cells to differentiate. This same group is typically activated by RA. “Notably, FGR induces the expression of genes targeted by RAR/RXR, such as cd38 and blr1, even without RA." To test its potential use in treatment-resistant leukemias, the researchers introduced FGR into RA-resistant HL-60 cells. In these, FGR did not cause the same maturation process, which suggests that there are other problems with cell signaling that stop both the RA and FGR pathways. This result highlights the complexity of resistance mechanisms and the need for additional research. These findings challenge the traditional view of FGR as strictly a cancer-driving protein. Instead, in this specific context, it appears to initiate anti-cancer behavior. That a single protein can reproduce the effects of a complex therapeutic compound like RA is both surprising and promising. If future research confirms this study's results in more advanced models, FGR could become a new tool for developing therapies for AML and potentially other blood cancers. DOI - https://doi.org/10.18632/oncotarget.28705 Correspondence to - Andrew Yen - ay13@cornell.edu Video short - https://www.youtube.com/watch?v=v2fjeFFoUPQ Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Oncotarget
NSD2 Gene Drives Cancer Cell Identity in Multiple Myeloma

Oncotarget

Play Episode Listen Later Mar 25, 2025 4:39


BUFFALO, NY - April 2, 2025 – A new #research paper was #published in Oncotarget, Volume 16, on March 21, 2025, titled “NSD2-epigenomic reprogramming and maintenance of plasma cell phenotype in t(4;14) myeloma." Researchers Andrea Gunnell, Scott T. Kimber, Richard Houlston, and Martin Kaiser from The Institute of Cancer Research, London, studied how a gene called NSD2 affects the behavior of multiple myeloma (MM) cells. Their findings reveal that NSD2 plays a key role in helping cancer cells retain their identity as plasma cells—white blood cells that normally help the immune system fight infections. This discovery could shape future treatment strategies for patients with a high-risk form of MM known as t(4;14) myeloma. Multiple myeloma is a type of blood cancer that begins in plasma cells found in the bone marrow. About 20% of patients have a genetic change called t(4;14), which makes the NSD2 gene highly active. The research team compared two types of myeloma cells: one with high NSD2 activity and one where NSD2 was turned off. They found that when NSD2 is active, it changes how DNA is folded and how genes are switched on or off, especially genes that help the cells act like plasma cells. When NSD2 was turned off, important markers like CD38 were reduced, and other genes normally silent in plasma cells were activated. The study indicated that NSD2 does not directly affect the main genes responsible for plasma cell creation. Instead, it influences many other genes that help maintain the cancer cell's identity, which contributes to cancer growth and survival. The researchers also observed physical changes in the cancer cells. Cells with active NSD2 looked and behaved more like typical plasma cells, while cells without NSD2 appeared more immature and lost important surface markers. These changes were linked to differences in how the DNA was organized inside the cells. These findings are especially important as new drugs are being developed to block NSD2. The study suggests that turning off NSD2 could change how MM cells respond to existing treatments. For example, if NSD2 is blocked and CD38 levels drop, the change might affect therapies that target CD38. However, the rise of other immune-related genes might make certain immunotherapies more effective. “Identifying the biological consequences of NSD2 over-expression in MM is not only relevant to informing new therapeutic interventions through indirect targeting of downstream effectors, but also to anticipate possible consequences of targeting NSD2 directly.” In summary, this study shows how NSD2 helps myeloma cells keep their cancerous identity by reorganizing the DNA and influencing gene activity. Understanding this role could help researchers design better treatment approaches and possibly overcome resistance to current therapies in t(4;14) myeloma. DOI - https://doi.org/10.18632/oncotarget.28706 Correspondence to - Andrea Gunnell - andrea.gunnell@icr.ac.uk Video short - https://www.youtube.com/watch?v=hibkjUpRq7I Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

CME in Minutes: Education in Primary Care
Thomas Martin, MD - Focusing on the Frontline: The Impact of Anti-CD38-Based Quadruplet Regimens for Transplant-Ineligible, Newly-Diagnosed Myeloma

CME in Minutes: Education in Primary Care

Play Episode Listen Later Mar 7, 2025 15:13


Please visit answersincme.com/BCK860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in myeloma discusses the latest data in anti-CD38 quadruplet regimens in newly diagnosed multiple myeloma. Upon completion of this activity, participants should be better able to: Identify the role of anti-CD38 monoclonal antibody (mAB)–based quadruplet regimens in the treatment landscape for newly diagnosed multiple myeloma (NDMM); Review the latest clinical data of anti-CD38 mAB-based quadruplet regimens for transplant-ineligible patients with NDMM; and Analyze evidence-based strategies for optimizing outcomes with anti-CD38 mAB-based quadruplet regimens in patients with transplant-ineligible NDMM.

The Human Upgrade with Dave Asprey
The Secret Molecule for Endless Energy | Dr. Andrew Salzman : 1253

The Human Upgrade with Dave Asprey

Play Episode Listen Later Feb 21, 2025 84:01


Could a single molecule be the difference between vibrant longevity and early decline? Dr. Andy Salzman—Harvard-trained physician, scientist, and creator of the first PARP1 inhibitor—joins Dave to reveal the real key to living longer, fighting disease, and maximizing your energy: NAD. This master molecule fuels your mitochondria, DNA repair, and cellular resilience, but here's the catch—it plummets as you age. That means more fatigue, brain fog, inflammation, and higher risks of disease. But what if you could stop the decline and even reverse it? Dr. Salzman breaks down the game-changing science behind NAD, CD38, and cellular repair—and the fastest, most effective ways to optimize your levels for peak performance, health, and longevity. Get ready to rethink everything you thought you knew about aging, pharmaceuticals vs. supplements, and the radical new approach to living better, longer. What You'll Learn: • The #1 reason your NAD is disappearing—and how to fix it • Why NAD is the missing link in energy, DNA repair, and disease prevention • The hidden enzyme (CD38) that's sabotaging your longevity • How to supercharge mitochondria, optimize blood flow, and fight aging at the source • Why the supplement industry has it wrong—and the best way to boost NAD naturally • The shocking truth about the FDA, pharmaceuticals, and the future of anti-aging medicine Resources: • Dave Asprey's New Book - Heavily Meditated: https://daveasprey.com/heavily-meditated/ • Andrew Salzman's Instagram – https://www.instagram.com/andrew_salzman/?hl=en • 2025 Biohacking Conference: https://biohackingconference.com/2025 • Danger Coffee: https://dangercoffee.com • Dave Asprey's Website: https://daveasprey.com • Dave Asprey's Linktree: https://linktr.ee/daveasprey • Upgrade Collective – Join The Human Upgrade Podcast Live: https://www.ourupgradecollective.com • Own an Upgrade Labs: https://ownanupgradelabs.com • Upgrade Labs: https://upgradelabs.com • 40 Years of Zen – Neurofeedback Training for Advanced Cognitive Enhancement: https://40yearsofzen.com Timestamps: 00:00 Trailer 01:07 Introduction and Episode Overview 02:29 Meet Dr. Andy Salzman 02:36 From Physician to Researcher 03:39 Pharmaceuticals vs. Nutritionals 04:17 The Role of NAD in Longevity 06:32 Challenges in Longevity Research 12:58 Understanding NAD and PARP 14:34 NAD's Impact on Health 23:19 Gut Health and Longevity 27:43 Innovations in NAD Supplementation 41:27 Customer Feedback and Product Effectiveness 42:41 Surprising Benefits of NAD for Sexual Health 44:47 NAD and Vascular Health 48:46 NAD's Role in Aging and Longevity 54:03 NAD and Lifestyle Choices 01:03:02 NAD and Cognitive Function 01:06:18 NAD and Exercise 01:13:42 NAD and Sleep 01:21:54 Final Thoughts on NAD and Longevity See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Research To Practice | Oncology Videos
Multiple Myeloma — Optimizing the Selection of First-Line Therapy with Dr Saad Zafar Usmani

Research To Practice | Oncology Videos

Play Episode Listen Later Feb 6, 2025 46:31


Featuring an interview with Dr Saad Zafar Usmani, including the following topics: Optimizing treatment intervention for patients with newly diagnosed multiple myeloma (MM) (0:00) Role of anti-CD38 antibodies in induction and maintenance therapy for patients with newly diagnosed disease (4:22) Case: A woman in her late 70s with revised International Staging System (R-ISS) Stage II IgG kappa myeloma who received D-Rd followed by maintenance daratumumab (14:02) Case: A man in his early 60s with double-hit myeloma who received D-KRd and carfilzomib maintenance therapy (26:10) Case: A man in his early 70s with R-ISS Stage III IgG kappa myeloma and translocation (4;14) who deferred transplant (33:24) Future directions in the management of MM (40:37) CME information and select publications  

Conscious Fertility
94: NAD and Fertility: Dr. Nichola Conlon on Mitochondrial Health and Anti-Aging

Conscious Fertility

Play Episode Listen Later Feb 3, 2025 81:54


In this episode, Dr. Nichola Conlon, a molecular biologist specializing in cellular aging, joins the Conscious Fertility Podcast to explore the pivotal role of NAD (nicotinamide adenine dinucleotide) and mitochondrial health in fertility and overall cellular vitality. Dr. Conlon explains how declining NAD levels with age can impact mitochondrial function, leading to fatigue, inflammation, and impaired cellular repair—factors that influence reproductive health and biological aging.We discuss how chronic inflammation depletes NAD levels and why relying solely on NAD precursors like NMN and NR may not be enough. Discover a whole-systems approach to restoring the body's natural ability to produce and recycle NAD, supporting energy production, mitochondrial function, and optimal fertility outcomes.Key takeaways:NAD is essential for energy production in our cells and mitochondrial function.NAD declines with age, contributing to aging and cellular dysfunction.Chronic inflammation (e.g., elevated CD38) can exacerbate NAD depletion.NAD boosting is most effective when addressing the root causes of decline, rather than simply adding precursors.A whole-systems approach to NAD supplementation, as seen in Nuchido Time Plus, helps address both NAD production and its proper recycling.Dr. Nichola Conlon's Bio: Dr Nichola Conlon is a molecular biologist specialising in the study of cellular aging. After a career in drug development, she founded Nuchido Laboratories to deliver disruptive innovation in the field of aging, rejuvenation and healthspan. Dr Conlon has a passion for sharing the latest science and is an accomplished speaker, with a skill for translating advanced science to help educate and support the wider population, encouraging people to age well and achieve their optimal life experience. Where To Find Dr. Nichola Conlon: Website: https://nuchido.com/(Use code LORNE20 for 20% off first order)Youtube: https://www.youtube.com/@nuchido2094Instagram:https://www.instagram.com/nuchido/Facebook: https://www.facebook.com/nuchidoHow to connect to Lorne Brown online and in person (Vancouver, BC)Acubalance.ca book virtual or in person conscious work sessions with Dr. Lorne Brown Lornebrown.comConscious hacks and tools to optimize your fertility by Dr. Lorne Brown:https://acubalance.ca/conscious-work/Download a free copy of the Acubalance Fertility Diet & Recipes and a copy of the ebook 5 Ways to Maximize Your Chances of Getting Pregnant from Acubalance.caConnect with Lorne and the podcast on Instagram:

Blood Cancer Talks
Episode 55. ASH 2024 Myeloma Updates with Dr. Rakesh Popat

Blood Cancer Talks

Play Episode Listen Later Jan 11, 2025 38:26


In this episode, we dive into the hottest updates in myeloma and amyloidosis at ASH 2024 annual meeting with Dr. Rakesh Popat. Here are the abstracts we discussed: 1. AQUILA Trial in High-Risk SMMOverview of the AQUILA trial testing single-agent daratumumab for high-risk smoldering multiple myeloma (HR-SMM) versus active monitoring. Discussion on patient characteristics, primary endpoints, and results showing significant progression-free survival (PFS) benefit with Dara. Insights into modes of progression, adequacy of active surveillance, and post-protocol therapy in control arm. Read the abstract. Read the simultaneous publication at NEJM. 2. Anito-Cel: New BCMA CAR T Therapy Early data from the iMMagine-1 trial showing strong efficacy and a promising safety profile for Anito-Cel, a novel BCMA CAR T. Discussion of its potential to rival cilta-cel while avoiding neurotoxicity concerns. Read the abstract.3. CARTITUDE-4 Update Updates on MRD-negativity rates and survival outcomes for cilta-cel in relapsed myeloma, with significant benefits over standard care. Read the abstract.4. ANDROMEDA OS Data in AL Amyloidosis Long-term data showing an overall survival (OS) benefit of Dara-VCd over VCd in AL amyloidosis. Insights into cardiac responses and crossover impact. Read the abstract.5. OPTIMUM Trial in Ultra-High-Risk NDMMFive-year follow-up of a tailored approach for ultra-high-risk newly diagnosed myeloma patients with continuous therapy incorporating multiple active agents. Subgroup outcomes highlighting both challenges and exceptional results. Read the abstract6. GMMG-HD7 Trial PFS Update Phase 3 trial results on Isa-VRD vs. VRD induction and risk-adapted tandem ASCT. Discussion on the role of CD38 in maintenance therapy. Read the abstract Read the simultaneous publication at JCO7. Exciting New Drugs Review of three innovative therapies: inobrodib, a BCMA-CD38 trispecific antibody, and cevostamab, a FcRH5-targeted bispecific antibody. Expert insights into their efficacy and potential to reshape myeloma care. Read the abstract

Oncology Brothers
Multiple Myeloma ASH 2024 Highlights with Dr. Robert Orlowski

Oncology Brothers

Play Episode Listen Later Jan 7, 2025 22:18


Welcome to another episode of the Oncology Brothers podcast! In this episode, hosts Drs. Rahul and Rohit Gosain are joined by Dr. Robert Orlowski from MD Anderson Cancer Center to discuss groundbreaking studies presented at ASH 2024 focused on multiple myeloma. We dived into four key studies: 1.⁠ ⁠AQUILA: Explore the impact of early intervention using daratumumab for smoldering myeloma, which showed improved progression-free survival (PFS) and overall survival (OS). 2.⁠ ⁠Dara Based Quad Therapy: We discuss a meta-analysis reaffirming the use of quadruplet therapy with anti-CD38 for newly diagnosed multiple myeloma as the standard of care. 3.⁠ CARTITUDE-4: study highlights the benefits of CAR-T therapy in earlier lines of treatment for patients with lenalidomide-refractory disease. 4.⁠ ⁠Role of IVIG with BCMA Bispecific Antibodies: Discover how IVIG can reduce infection rates and improve overall survival when used alongside BCMA-targeted therapies. Tune in for an insightful discussion that will enhance your understanding of the latest advancements in multiple myeloma treatment. Don't forget to check out our other episodes on CLL, myeloma, and lymphoma from ASH 2024! Subscribe to the Oncology Brothers for more updates and expert insights in oncology! Website: http://www.oncbrothers.com/  X/Twitter: https://twitter.com/oncbrothers  Contact us at info@oncbrothers.com

The Doctor's Farmacy with Mark Hyman, M.D.
Reverse Aging Now: The Latest Longevity Breakthroughs | Dr. Eric Verdin

The Doctor's Farmacy with Mark Hyman, M.D.

Play Episode Listen Later Dec 4, 2024 72:39


What if aging wasn't inevitable, but something you could slow—or even reverse? In this episode of “The Dr. Hyman Show,” Dr. Eric Verdin, the president of the Buck Institute for Research on Aging, and I dive deep into the science of longevity. Discover how lifestyle choices, mitochondrial health, and cutting-edge research are transforming our understanding of aging. From fasting and nutrient sensing to emerging therapies like CD38 inhibitors, this episode reveals actionable insights to help you live a longer, healthier life. In this episode, we discuss: The Role of Mitochondria in Aging The Critical Role of NAD Levels and Aging Lifestyle Interventions for Longevity Gene Therapy The Importance of CD38 and Enzyme Inhibition View Show Notes From This Episode Get Free Weekly Health Tips from Dr. Hyman Sign Up for Dr. Hyman's Weekly Longevity Journal This episode is brought to you by Rupa Health, BIOptimizers, LMNT, and Fatty 15. Streamline your lab orders with Rupa Health. Access more than 3,500 specialty lab tests and register for a FREE live demo at RupaHealth.com. Don't let stress take over your holidays. Try Magnesium Breakthrough from BiOptimizers. Head to Bioptimizers.com/Hyman and use code HYMAN10 to save 10%. LMNT is giving listeners a FREE eight-count sample pack of their vital electrolyte drink mix with any purchase. Just visit DrinkLMNT.com/Hyman today. Fatty15 contains pure, award-winning C15:0 in a bioavailable form. Get an exclusive 15% off a 90-day starter kit subscription. Just visit Fatty15.com and use code DRHYMAN10 to get started. Learn more about your ad choices. Visit megaphone.fm/adchoices

ScienceLink
Lo mejor de la reunión anual de la sociedad de hematología oncológica (SOHO) 2024

ScienceLink

Play Episode Listen Later Nov 27, 2024 14:33


La Dra. Nidia Paulina Zapata Canto, hematóloga adscrita al Instituto Nacional de Cancerología en la Ciudad de México, México, en este episodio de “Preguntémosle al experto…” nos comenta sobre lo más destacado durante la reunión anual de la sociedad de hematología oncológica (SOHO) 2024. Leucemia aguda mieloblástica  Inteligencia artificial: El Dr. Torsten Haferlach nos comenta que la medicina está entrando en una nueva era revolucionaria, en la que la inteligencia artificial juega un papel cada vez más fundamental en los procesos, el diagnóstico y los tratamientos. Biología molecular: La implementación en países como Brasil, Perú, Uruguay, Chile y Paraguay tiene como objetivo analizar los paneles de secuenciación, lo que permitirá obtener más información sobre cómo las mutaciones varían en cada región debido a diversos factores. Leucemia aguda linfoblástica    La calaspargasa pegol es una forma modificada de la enzima L-asparaginasa, utilizada en el tratamiento de la leucemia linfoblástica aguda. Una de sus características destacadas es su vida media prolongada de aproximadamente 16 días, lo que permite una dosificación menos frecuente en comparación con otras formulaciones de asparaginasa.   Alliance: Estudio de inotuzumab ozogamicina seguido de blinatumomab para la leucemia linfoblástica aguda de linaje B, Ph-negativa y CD22-positiva en adultos mayores recién diagnosticados o adultos con enfermedad recidivante o refractaria.   Neoplasias proliferativas   COMFORT-I y COMFORT-II: Fueron estudios fundamentales que llevaron a la aprobación de ruxolitinib en pacientes con mielofibrosis. El COMFORT-I fue una comparación de ruxolitinib versus placebo en pacientes con mielofibrosis que no habían recibido inhibidores de JAK, y el COMFORT-II fue un estudio similar con ruxolitinib versus la mejor terapia alternativa en pacientes que no habían recibido inhibidores de JAK.  JAKARTA: Resultados actualizados del estudio de fedratinib en pacientes con mielofibrosis de riesgo intermedio-2 o alto.  SIMPLIFY-1: Estudio de momelotinib vs. ruxolitinib en pacientes con mielofibrosis que no han recibido inhibidores de la cinasa Janus. Mieloma múltiple  KarMMa-3: Estudio que evaluó idecabtagén vicleucel en comparación con regímenes estándar en pacientes con mieloma múltiple recidivante y refractario que han recibido de dos a cuatro líneas de tratamiento previas, incluido un agente inmunomodulador, un inhibidor del proteasoma y un anticuerpo monoclonal anti-CD38, y fueron refractarios al último régimen de tratamiento.   CARTITUDE 1: Estudio que evalúa ciltacabtagene autoleucel, una terapia de células T dirigida al receptor de antígeno quimérico de maduración de células B en pacientes con mieloma múltiple en recaída o refractario.   Leucemia linfocítica crónica   La transformación de Richter es una complicación poco frecuente pero agresiva de la leucemia linfocítica crónica en la que las células de LLC se convierten en un linfoma de alto grado, generalmente un linfoma difuso de células B grandes.   Entre otros...       Fecha de grabación: 13 de septiembre de 2024.                                 Todos los comentarios emitidos por los participantes son a título personal y no reflejan la opinión de ScienceLink u otros. Se deberá revisar las indicaciones aprobadas en el país para cada uno de los tratamientos y medicamentos comentados. Las opiniones vertidas en este programa son responsabilidad de los participantes o entrevistados, ScienceLink las ha incluido con fines educativos. Este material está dirigido a profesionales de la salud exclusivamente.

Authentic Biochemistry
Immune Cell Biochemistry II. B lymphocytes. c.21. CD38 NAD+ hydrolase mediates the Inflammatory Response Authentic Biochemistry Podcast Dr. Daniel J. Guerra 16.7.24

Authentic Biochemistry

Play Episode Listen Later Jul 17, 2024 61:06


References Cells 2020, 9(1), 228 Front. Immunol. 2020. vol 11. 29 November. FEBS 2013. Volume280, Issue15 August:3530-3541 Cell Metabolism 2016. 23, 1127–1139 Beethoven. LV . 1800. Septett Es-Dur op. 20 https://youtu.be/pXsj43qCcUA?si=r5vW4PpfzvywF9b3  Jacques Revaux  Gilles Thibaut and Claude François 1967. "My Way". Sinatra https://youtu.be/qQzdAsjWGPg?si=YWKurvGp9Xt0TYK1 --- Support this podcast: https://podcasters.spotify.com/pod/show/dr-daniel-j-guerra/support

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast
Prof. Mohamad Mohty, MD, PhD - Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jul 3, 2024 48:30


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QTT865. CME credit will be available until July 18, 2025.Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sanofi.Disclosure information is available at the beginning of the video presentation.

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast
Prof. Mohamad Mohty, MD, PhD - Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Jul 3, 2024 48:32


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QTT865. CME credit will be available until July 18, 2025.Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sanofi.Disclosure information is available at the beginning of the video presentation.

PeerView Internal Medicine CME/CNE/CPE Video Podcast
Prof. Mohamad Mohty, MD, PhD - Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms

PeerView Internal Medicine CME/CNE/CPE Video Podcast

Play Episode Listen Later Jul 3, 2024 48:32


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QTT865. CME credit will be available until July 18, 2025.Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sanofi.Disclosure information is available at the beginning of the video presentation.

PeerView Internal Medicine CME/CNE/CPE Audio Podcast
Prof. Mohamad Mohty, MD, PhD - Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms

PeerView Internal Medicine CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jul 3, 2024 48:30


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QTT865. CME credit will be available until July 18, 2025.Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sanofi.Disclosure information is available at the beginning of the video presentation.

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast
Prof. Mohamad Mohty, MD, PhD - Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jul 3, 2024 48:30


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QTT865. CME credit will be available until July 18, 2025.Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sanofi.Disclosure information is available at the beginning of the video presentation.

PeerView Clinical Pharmacology CME/CNE/CPE Video
Prof. Mohamad Mohty, MD, PhD - Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms

PeerView Clinical Pharmacology CME/CNE/CPE Video

Play Episode Listen Later Jul 3, 2024 48:32


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QTT865. CME credit will be available until July 18, 2025.Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sanofi.Disclosure information is available at the beginning of the video presentation.

PeerView Immunology & Transplantation CME/CNE/CPE Audio Podcast
Prof. Mohamad Mohty, MD, PhD - Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms

PeerView Immunology & Transplantation CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jul 3, 2024 48:30


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/QTT865. CME credit will be available until July 18, 2025.Expanding Frontline Frontiers in MM: Insights on Delivering Modern Care With Innovative CD38 Quadruplet Platforms In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sanofi.Disclosure information is available at the beginning of the video presentation.

CME in Minutes: Education in Primary Care
Saad Z. Usmani, MD, MBA, FACP, FASCO - Making the Case for Triple Therapy in R/R Multiple Myeloma: Expert Guidance for Optimizing Anti-CD38 mAb Regimens

CME in Minutes: Education in Primary Care

Play Episode Listen Later Jun 25, 2024 14:57


Please visit answersincme.com/AEP860 to participate, download slides and supporting materials, complete the post test, and obtain credit. In this activity, an expert in myeloma discusses strategies to integrate novel anti-CD38 monoclonal antibody (mAb)-based triplet regimens into care plans for patients with early relapse multiple myeloma (MM). Upon completion of this activity, participants should be better able to: Review the latest evidence-based guideline recommendations for the treatment of early relapse MM; Outline the clinical implications of the latest evidence for anti-CD38 mAb-based triplet regimens in the treatment of early relapse MM; and Identify strategies to optimally integrate novel anti-CD38 mAb-based triplet regimens into treatment plans for patients with early relapse MM.

ASCO Daily News
Enhancing Treatment Efficacy in Multiple Myeloma at ASCO24

ASCO Daily News

Play Episode Listen Later Jun 24, 2024 22:10


Drs. John Sweetenham and Marc Braunstein discuss practice-changing studies in hematologic malignancies that were featured at the 2024 ASCO Annual Meeting, including the ASC4FIRST trial in chronic myeloid leukemia and IMROZ and CARTITUDE-4 in multiple myeloma.  TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham from UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News Podcast. On today's episode, we'll be discussing practice-changing abstracts and other key advances in hematological malignancies that were featured at the 2024 ASCO Annual Meeting. Joining me for this discussion is an old friend, Dr. Marc Braunstein, a hematologist and oncologist from the NYU Langone Perlmutter Cancer Center.  Our full disclosures are available in the transcript of this episode. Marc, it's great to have you back on the podcast again. There were some important studies in the heme space at the Annual Meeting this year, and we're very pleased that you're able to share your takeaways.  Dr. Marc Braunstein: Thank you, John. It's great to be back again. Dr. John Sweetenham: Let's start out, Marc, with LBA6500. This abstract reports the primary results of the ASC4FIRST trial, and this was a trial comparing asciminib with investigator selected tyrosine kinase inhibitors in newly diagnosed patients with chronic myeloid leukemia. Could you tell us a little about the trial and how you think it's going to impact clinical practice? Dr. Marc Braunstein: Absolutely. So, asciminib is an oral tyrosine kinase of the ABL kinase domain. As we know in CML, the BCR-ABL translocation is characteristic of the disease, and asciminib is approved for chronic phase CML with a T315I resistance mutation or for patients who have received 2 or more prior lines of therapy. So the ASC4FIRST trial was a randomized trial of 405 patients with newly diagnosed chronic phase CML who are randomized one to one to receive either asciminib at 80 milligrams once daily, or investigator's choice of a first generation TKI imatinib or one of three second generation TKIs nilotinib, dasatinib, or bosutinib. The primary endpoint of the study was the major molecular response, or MMR, at 48 weeks. Pretty much, the study met its primary endpoint with a 67% rate of MMR at 48 weeks, with asciminib versus 49% in patients treated with the investigator's choice of TKI. And in addition, the major molecular remission or MMR of 4.5, which is a deep remission, those rates were higher as well, with asciminib versus investigator's choice at a rate of 39% versus 21% when comparing the groups. Furthermore, when we looked at toxicity, there were fewer grade 3 or higher adverse events, with the asciminib at 38% versus either 44% with the first generation, or 55% with the second generation TKI, and fewer discontinuations as well with asciminib.  So I think this abstract is practice-changing. I think it offers compelling data to use asciminib upfront for chronic phase CML. Those who don't agree with that sentiment might argue that we want to see longer term follow up. There's a planned follow-up at 96 weeks. We would want to see the rate of progression to acute myeloid leukemia and of course overall survival as well. But I think the abstract certainly shows an improvement in outcomes with asciminib versus our current array of TKIs. Dr. John Sweetenham: Yeah, I think it certainly is, at least at minimum, potentially practice changing. I agree with you. Just one question, and this may be a little bit speculative, but do you have any thoughts about treatment free survival with asciminib and how that might line up against some of the other TKIs? Dr. Marc Braunstein: Yeah, that's a great question. The abstract did not necessarily address that, patients were treated until progression, but we know that with the current landscape of TKIs, that in patients who have achieved a deep MR of 4 or 4.5 for at least 2 years who discontinue their TKI, the rate of relapse is about 50%. The current study, the ASC4FIRST, doesn't address that, but I think it's a really good question about whether, for those patients who have achieved a deep remission, whether they can eventually stop asciminib down the line. Dr. John Sweetenham: Yeah, I guess it's one of those ‘watch this space' things.  So we'll see how the data mature out. And let's move on to what I think is another potentially practice-changing study, at least in certain parts of the world. And that's [the] LBA7000 study in classical Hodgkin lymphoma. As you remember, this was a German Hodgkin lymphoma study group trial which looked at the tolerability and efficacy of a novel regimen, BrECADD versus eBEACOPP for patients with advanced stage classical Hodgkin lymphoma in their study, which is known as GHSG HD21. Can you give us your thoughts and take home messages from this trial? Dr. Marc Braunstein: Yeah, John, absolutely. So the German HD21 study is a phase 3 study of 1,500 patients with classical Hodgkin lymphoma. The majority were stage 3 or 4, 84%, that compared two regimens BEACOPP to BrECADD. The major difference between these 2 groups being that the newer BrECADD regimen swaps out bleomycin for brentuximab vedotin, which is an anti-CD30 antibody drug conjugate. Also, in the BrECADD regimen they eliminate vincristine that's incorporated into BEACOPP. Those are kind of the global differences between these 2 regimens. And when comparing these, they looked at the primary endpoint of progression-free survival. Of note, in this study there was a PET adjusted approach where if patients achieved interim PET negativity after 2 cycles, that was followed by an additional 2 cycles of their treatment as opposed to 4 cycles if they were PET positive after the initial 2 cycles of their respective treatment. And of note, there were similar rates of PET2 negativity between both arms, about 58% in both arms.  So at a median follow-up of 48 months, the 4-year progression-free survival was significantly better with the brentuximab containing BrECADD regimen at 94% versus 91% with a hazard ratio of 0.66. And the overall survival of the BrECADD arm was 98.6%, which is very high and impressive. The 4-year overall survival was similar between the arms at around 98%, but of note, there were fewer severe adverse events with BrECADD, the brentuximab containing arm versus BEACOPP at about 42% versus 59% and interestingly less peripheral neuropathy with the brentuximab containing BrECADD. So we're doing extremely well in treating advanced stage classical Hodgkin lymphoma. So the bar is set very high. But in this study, the rates of progression-free survival and overall survival are very impressive.  While these intensive regimens tend to be used outside of the U.S., there are several notable benefits of the study, including greater than 50% PET2 negativity and high rates of progression-free survival at 4 years. In discussing this abstract, it's worth noting that there are other competing regimens, if you want to call it that, that are more commonly used in the U.S. So the ECHELON-1 study looked at brentuximab AVD compared with ABVD with bleomycin and it was a 94% versus 89% 6-year overall survival rate favoring the brentuximab containing A+AVD regimen. And lastly, more recently, the SWOG S1826 study that hasn't been published but was presented in abstract form looked at nivolumab AVD versus brentuximab AVD at a median follow up of 12 months showed a progression-free survival of 94% versus 86%. And that study still has yet to be published and needs to mature. But both of those regimens are in the NCCN guidelines. So, we're definitely pushing the bar higher in terms of improving responses in treating advanced classical Hodgkin lymphoma. Dr. John Sweetenham: I think that there's no question that these results from BrECADD are very impressive. But I'm taken back to what I think has been a kind of philosophic discussion in Hodgkin lymphoma now for a number of years about balancing disease control and efficacy against the potential short-term and long-term toxicity of the regimens, particularly when you have very effective salvage therapies for those patients who may suffer a relapse. So I think that this is a discussion over whether you take a very intensive, upfront approach to Hodgkin lymphoma versus something that may be less and slightly less intensive. I suspect that's a discussion that's going to continue for a long time. I don't know what you feel, but my own feeling about this is that this study will likely have a major influence over treatment of Hodgkin lymphoma, particularly in western Europe. Less likely in the US.., I would think. I don't know what your thoughts about that are. Dr. Marc Braunstein: Well, it's a great question. In SWOG S1826, that study did include pediatric patients. In HD21, the median age was 31 and did not include pediatric patients. So I think we have to be selective in terms of fitness and which patients may be better suited for different regimens. But I think what all these studies show is certainly when we incorporate novel immunotherapies, whether it's brentuximab vedotin, nivolumab, we improve progression-free survival and even overall survival. Dr. John Sweetenham: Absolutely.  So let's shift gears now and take a look at Abstract 7500, the IMROZ study. This was the study of isatuximab, bortezomib, lenalidomide and dexamethasone versus VRD alone for transplant ineligible patients with newly diagnosed multiple myeloma. I know we discussed this in our preview podcast a few weeks back, Marc, but I just wonder now, having seen the data in more detail, what do you think of the important takeaways? And again, are we looking at a new standard of care? Dr. Marc Braunstein: You know, there are many standards of care in multiple myeloma, but we're always looking to make improvements on the regimens we have at our disposal. So, just to recap, IMROZ is a phase 3 randomized study of the anti-CD38 monoclonal antibody isatuximab with the backbone of bortezomib, lenalidomide, dexamethasone or VRD versus VRD alone, specifically, in transplant ineligible newly diagnosed multiple myeloma patients age less than 80. They studied 446 patients in this study, randomized 3 to 2 to Isa-VRD versus VRD alone, with the primary endpoint of progression free survival. Now, similar to other studies where they included a monoclonal antibody up front, the study met its primary endpoint of improving progression-free survival with the quad regimen containing the monoclonal antibody isatuximab versus VRD alone.  So what was interesting about the study, it's really the first of its kind to be presented that specifically looked at transplant ineligible patients, which is presumably a less fit or perhaps more frail population that wouldn't go on to consolidation with stem cell transplant. And in this study, the progression-free survival at 5 years was 63% versus 45%, clearly superior when you included isatuximab. And the rates of complete remission and MRD negativity were all significantly improved, too. However, that was also met with slightly more grade 3 or higher treatment emergent adverse events, 92% versus 84% in the control arm. There are also 11% grade 5 treatment emergent adverse events with the isatuximab group versus 5.5% with VRD alone. Although there was no major difference in treatment discontinuation. One small caveat worth noting, too, is that high-risk patients in this study, when presented at ASCO, did not necessarily show a difference in benefit, although there wasn't necessarily a detriment either.  So, John, I think that clearly quadruplet regimens are superior in outcomes of efficacy to triplets, even in transplant-ineligible patients. But I think we have to tailor these treatments to individual patients because I think when it comes to transplant-ineligible patients, it's a spectrum of patients who may be more or less fit for quad regimens versus triplet regimens. It's also worth noting, though, that in this study, the patients are really only getting a quad regimen for 4 cycles. They get their Isa-VRD, and then you drop the bortezomib.  So when we think about quads, it's not that they're getting the quad regimen indefinitely, it's really for the induction cycles. But still, I think we have to be aware of potential safety issues. Dr. John Sweetenham: Okay, great. And let's stay on the theme of multiple myeloma, Marc, and talk a little bit about Abstract 7504, which was a subgroup analysis of the CARTITUDE-4 study. This is a report on the use of ciltacabtagene autoleucel versus standard of care in patients with functional high risk multiple myeloma. Can you give us your thoughts on this and maybe put it into a bit of context for us?  Dr. Marc Braunstein: Absolutely, John. It's really a great time to be in the field of multiple myeloma. We're making tremendous progress, but when we think about one of the unmet needs, it's just consistently the high-risk patients who have shorter responses and are at higher risk for poorer outcomes. Just to review, cilta-cel is one of the 2 available anti-BCMA CAR T-cell products available for the treatment of relapsed or refractory multiple myeloma. Very recently, the FDA approved cilta-cel for lenalidomide refractory patients after 2 or more prior lines of therapy based on the CARTITUDE-4 study, which was published by San-Miguel and colleagues in New England Journal of Medicine in July 2023. And that study randomized 419 patients with multiple myeloma with 1 to 3 prior lines of therapy to receive either cilta-cel or physician's choice of standard of care, which was either 1 of 2 triplet regimens, a pomalidomide, bortezomib, dexamethasone or daratumumab, pomalidomide and dexamethasone. It's worth noting that about 25% of the patients in the CARTITUDE-4 study had prior anti-CD38 antibody treatment previously and the carfilzomib was not included in one of the standard-of-care arms, and we know that those regimens containing carfilzomib do increase survival in relapsed myeloma.  Nevertheless, the primary outcome of progression-free survival was not reached in the CAR T-cell arm versus 11.8 months in the standard-of-care arm, with a significant reduction in progression of 74%. So clearly a positive study and CAR T-cell therapy is included in the NCCN guidelines for patients who have an early relapse from their myeloma. The current abstract by Costa et al focused specifically on a subgroup of 79 patients from CARTITUDE-4 in second line of treatment and looked at what they called functional high-risk myeloma, defined as progression of disease within 18 months of initial treatment or after stem cell transplant. Again, the study showed a retained benefit of cilta-cel with significant improvement in progression-free survival either not reached or 12 months with the control standard of care arm, as well as complete remission rate and rates of MRD negativity of 65% versus 10% in the control.  The overall survival outcome was still immature and not presented. Nevertheless, cilta-cel is clearly superior to standard-of-care triplet regimens. I think that for patients with high risk, they clearly derive a benefit from CAR T-cell therapy if they have short progression-free survival after initial therapy.  Dr. John Sweetenham: Thanks, Marc. So let's round this out by talking about another area of unmet need, I guess in a way in a difficult to treat patient group. And that's Abstract 7007, the SYMPATICO study. This is a study which looks at the efficacy and safety of ibrutinib and venetoclax in patients with mantle cell lymphoma who had a mutated TP53. Can you just briefly review this for us and tell us what you think we should be taking away from this studys? Dr. Marc Braunstein: So, mantle cell lymphoma typically has an aggressive behavior, but the subgroup of patients with a P53 mutation tend to have the poorest outcomes and do represent an area of unmet need. Although BTK inhibitors are making important improvements in mantle cell lymphoma, they have yet to be approved in newly diagnosed mantle cell lymphoma. Acalibutinib and zanubrutinib are FDA-approved BTK inhibitors for previously treated mantle cell lymphoma. Ibrutinib was withdrawn from the market in the U.S. for mantle cell lymphoma. Dr. Michael Wang's group presented late-breaking data from the phase 3 SYMPATICO trial at ASH 2023, in which 267 patients with relapsed refractory mantle cell lymphoma were randomized to receive either ibrutinib plus the BCL2 inhibitor venetoclax or ibrutinib plus placebo after 1 to 5 prior lines of therapy. And that study showed a 32 versus 22 months progression-free survival at a median follow up of 51 months. The current abstract, also by Dr. Wang and colleagues, looked at the subgroup of patients who had a P53 mutation and included an open label cohort of 44 patients in the first line of treatment and a relapse refractory cohort of 75 patients, and compared this subgroup of patients with P53 mutation to those without. When we look at the outcomes, the patients who did not have a P53 mutation clearly did better in terms of progression-free survival being not reached in first-line treatment compared to 22 months progression-free survival in those patients with first-line [treatment] with a P53 mutation. As well as in the relapsed refractory setting, the PFS without the P53 mutation was 47 months versus 21 months with the mutation. However, when you look at these patients treated with ibrutinib and venetoclax comparing whether they got treated in first line or the relapse refractory setting, the overall response rates are very similar at about 80% to 90% and the CR rates were very similar at about 55% to 58%, which to me suggests that although patients with P53 mutation do worse than those without it, whether they're treated in the first-line or the relapse setting with this combination of venetoclax, they tend to do somewhat similar, suggesting that you can overcome resistance to prior therapy in the relapse setting. So I think further data are certainly warranted to explore the role of combination therapies that include novel agents such as BTK inhibitors in the first line setting.  It's worth noting that the TRIANGLE study was recently published, and this study looked at including ibrutinib at various phases, including at induction in combination with intensive chemotherapy and during the maintenance phase. And that study showed encouraging outcomes in patients who received ibrutinib even without stem cell transplant compared to those who received stem cell transplant. So the role of BTKIs in mantle cell lymphoma is certainly evolving, and I think it offers a very effective intervention without the same kind of toxicities we see with cytotoxic chemotherapy that's traditionally used in mantle cell lymphoma. But I think the subgroup of patients with P53 mutation in this disease still represent an area of unmet need that unfortunately have worse outcomes. But novel agents may be able to overcome some of those adverse outcomes. Dr. John Sweetenham: Yeah, I agree. I think these are intriguing data, and obviously it needs more follow-up and probably more prospective studies. But nevertheless, I think there are some signals there for sure that need to be followed up on.  Marc, as always, it's great to have your insights on key advances in the heme space from ASCO. An important year this year, and we really appreciate your time and effort in sharing with us your thoughts on what we've learned this year. So thank you as always. Dr. Marc Braunstein: My pleasure. Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstract discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts.   Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's guest:  Dr. Marc Braunstein  @docbraunstein    Follow ASCO on social media:   @ASCO on Twitter   ASCO on Facebook   ASCO on LinkedIn     Disclosures:  Dr. John Sweetenham:  Consulting or Advisory Role: EMA Wellness  Dr. Marc Braunstein:  Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb/Celgene, Adaptive Biotechnologies, GlaxoSmithKline, ADC Therapeutics, Janssen Oncology, Abbvie, Guidepoint Global, Epizyme, Sanofi, CTI BioPharma Corp  Speakers' Bureau: Janssen Oncology  Research Funding (Institution): Janssen, Celgene/BMS   

NEJM This Week — Audio Summaries
NEJM This Week — June 20, 2024

NEJM This Week — Audio Summaries

Play Episode Listen Later Jun 19, 2024 33:09


Featuring articles on combination therapy for diffuse large B-cell lymphoma, autosomal dominant Alzheimer's disease, noninvasive ventilation for preoxygenation during emergency intubation, a novel anti-CD38 antibody in immune thrombocytopenia, and a glucose-responsive insulin for type 2 diabetes; a review article on congenital and acquired Chiari syndrome; a case report of a man with arthritis and rash; and Perspectives on ethics and innovative research on brain diseases, on sustaining and scaling up street medicine, and on the maternal crossroad.

Dr. Berg’s Healthy Keto and Intermittent Fasting Podcast

In this podcast, I'm going to tell you how to slow down aging so you can look younger and live longer. The mitochondria are the body's energy factory. The health and function of your mitochondria directly correlate to aging and longevity. The Krebs cycle is a process in your body that starts with food and ends with energy. It requires nutrients or cofactors to work properly. NAD is a vital nutrient involved in extracting energy from food to make ATP, and it's critical for longevity and anti-aging. NAD prevents muscle loss, especially in cancer patients, and protects against radiation. As we age, NAD decreases. Researchers have found that CD38 depletes NAD, and mice with less CD38 tend to live longer. Here are 5 compounds that boost NAD to help slow aging: 1. Apigenin Parsley is the best source, but it's also found in thyme, oregano, basil, and celery. 2. Anthoxanthin Consume blueberries and other blue, purple, or red foods such as elderberry, concord grapes, and purple potato. 3. Curcumin This is found in turmeric. 4. Quercetin The best source is onion, and the most is found in the outer part. You can also find quercetin in apple skin. 5. Methylene blue This was the first medical drug ever invented. It seems to be a good inhibitor of CD38, which can help boost NAD.

ASCO Daily News
Day 4: Top Takeaways From ASCO24

ASCO Daily News

Play Episode Listen Later Jun 3, 2024 10:57


Dr. John Sweetenham shares highlights from Day 4 of the 2024 ASCO Annual Meeting, including exciting new data from the IMROZ trial in multiple myeloma, adjuvant therapy for triple-negative breast cancer in A-BRAVE, and the front-line treatment of advanced renal cell carcinoma in JAVELIN Renal-101. TRANSCRIPT Dr. John Sweetenham: I'm Dr. John Sweetenham, the host of the ASCO Daily News Podcast, with my top takeaways on selected abstracts from Day 4 of the 2024 ASCO Annual Meeting.   Today's selection features 3 randomized prospective trials in the first-line treatment of multiple myeloma, adjuvant therapy for triple negative breast cancer, and the frontline treatment of advanced renal cell carcinoma, all of which provide important new data.   My full disclosures are available in the transcript of this episode. The first of today's abstracts is number 7500. This abstract, presented by Dr. Thierry Facon from the Department of Hematology at the University of Lille in France, describes the results of the IMROZ study. This was a multicenter phase 3 study comparing a current standard first-line regimen for transplant ineligible patients with myeloma VRd with the same combination plus an additional agent, isatuximab.  The combination of bortezomib, lenalidomide and dexamethasone, known as VRd, is currently a standard first-line regimen for patients with multiple myeloma, both transplant eligible and ineligible. Previous phase 3 studies have shown that the addition of an anti-CD38 antibody to triplet regimens improves outcomes in newly diagnosed patients. Based on early phase clinical trial data showing promising response rates with isatuximab, the IMROZ study was conducted to compare isatuximab VRd with VRd alone in patients who were either ineligible for transplant or had no immediate indication for transplant. IMROZ was a global study conducted in 21 countries that involved 446 patients randomly assigned 3:2 to induction therapy with Isa-VRd followed by continuous Isa-Rd or induction therapy with VRd followed by Rd alone. The rate of complete response or better was approximately 75% with Isa-VRd compared with 64% with VRd alone. Very good partial response or better was achieved in 89% of patients with Isa-VRd, compared with around 83% of those with VRd alone. With a median follow-up at 5 years, Isa-VRd followed by Isa-Rd had reduced the risk of progression or death by 40.4% compared with VRd alone. The 60-month progression-free survival rate was 63% for Isa-VRd compared with around 45% with VRd alone, and the progression-free survival benefit was maintained in most of the analyzed subgroups. Minimal residual disease negativity was also measured in this study in both the intent to treat population and those patients who achieved a complete response. For example, in the intent to treat population, the MRD negative rate was 58% with Isa-VRd compared with around 43% with VRd alone. There were also higher rates of sustained MRD negativity for 12 months or longer among patients assigned to Isa-VRd compared with VRd alone, reflecting deeper responses in the Isa-VRd arm. Although overall survival data is still immature, data from an interim analysis showed a favorable trend in the Isa-VRd arm with 22.4% risk reduction compared with VRd alone. There was little additional toxicity from the inclusion of isatuximab with the VRd regimen and the quality-of-life data were comparable and stable in both arms of the study. The investigators concluded that although overall survival data are immature, there is a trend in favor of Isa-VRd and this, combined with the favorable response, toxicity and progression-free survival data, establish isatuximab VRd as a potential new standard of care for newly diagnosed multiple myeloma patients not eligible for transplant. There was some discussion regarding the potential use of this regimen in patients over 80 years of age since the upper age limit was capped in IMROZ at 80 years. Although there are concerns for tolerance of the 4-drug regimen in the older patient group, it seems likely that this will be adopted, especially for those with good performance status and without major comorbidities.   Next up is LBA500. This abstract reports results of the A-BRAVE trial. This trial, presented by Dr. Pier Franco Conte from the University of Padova, Italy, was a phase 3 randomized trial to assess the efficacy of the immune checkpoint inhibitor avelumab in 2 groups of patients: those with early triple negative breast cancer, with residual disease after neoadjuvant chemotherapy; and those at high risk after primary surgery and adjuvant chemotherapy. As Dr. Conte explained in the introduction to this trial, there is a fairly compelling rationale for the use of checkpoint inhibitors in triple negative breast cancer. The disease has been shown to be more immunogenic than the other breast cancer types with immune biomarkers such as TILs and PDL-1 expression associated with better prognosis, added to which, data in metastatic breast cancer show a correlation between PDL-1 expression and checkpoint inhibitor response. In the A-BRAVE study, 477 high risk patients who had completed local, regional, and systemic treatment with curative intent were stratified according to adjuvant or post neoadjuvant status and randomized 1:1 to receive avelumab at 2-week intervals for 52 weeks or to observation only. Results of the study showed a non-statistically significant improvement in three-year disease-free survival in the overall intent to treat population at 5.1% and in the post neoadjuvant patients at 6.2%. Overall survival was a secondary endpoint in this trial. The results show a significant improvement in overall survival of 8.1% in the intent-to-treat population and a very similar improvement in the post-neoadjuvant patients. The authors reported good tolerance of avelumab, although in total almost 30% discontinued treatment at some point. In their conclusion, the investigators state that the 34% reduction in the risk of death suggests a potential role for avelumab in early triple negative breast cancer patients at high risk after primary surgery or with invasive disease after neoadjuvant chemotherapy. Correlative studies are planned on tumor plasma and feces in this study. These are interesting and somewhat tantalizing results, suggesting a real effect from avelumab. Although confounded somewhat by the sample size, it will be important to see how these results mature with further follow-up.   Today's third selected abstract is number 4508 reporting the final analysis of the JAVELIN Renal 101 phase 3 trial in patients with advanced renal cell carcinoma. This study compared the combination of axitinib plus avelumab with sunitinib in this patient group. The trial included 886 patients, of whom around 61% of those in the combination group and around 65% of those in the monotherapy group were PDL-1 positive. In the initial analysis from the JAVELIN Renal 101 study, after at least 6 months of follow-up, avelumab and axitinib significantly improved progression-free survival over sunitinib in patients with PDL-1 positive tumors and in the overall population with advanced renal cell carcinoma. In the fall cohort, the median progression-free survival with the combination was 13.8 months compared with only 8.4 months with sunitinib, and based on those results, the combination received FDA approval as a first-line treatment for patients with advanced renal cell carcinoma in May of 2019. The progression-free survival observed in the initial analysis was confirmed with a new long-term analysis in the overall population. Median progression-free survival with avelumab and axitinib was 13.9 months compared with only 8.5 months with sunitinib and the median duration of response with the combination was 19.4 months versus 14.5 months with sunitinib. However, no difference in overall survival was seen. At 60 months, the overall survival in the combination group was 38.8% and 36.2% with sunitinib. In patients who were PDL-1 positive at 60 months, overall survival with a combination was 37.1% compared with 33.4% with sunitinib.  Despite the sustained difference in progression-free survival seen with this combination, the discussant at this session pointed out that most oncologists are unlikely to recommend a combination which has not been shown to improve overall survival when published studies have reported on 4 combinations which do positively impact overall survival in this patient group. Despite the good tolerance of this regimen, it seems unlikely to be a preferred frontline regimen in advanced renal carcinoma moving forward.  That concludes today's report. Thanks for listening and we hope you have enjoyed listening to our top takeaways from ASCO24. If you value the insights that you hear on the ASCO Daily News Podcast, please remember to rate, review and subscribe wherever you get your podcasts.   Disclaimer:  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow ASCO on social media:   @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures: Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast
Suzanne Lentzsch, MD, PhD / Joshua Richter, MD - “Four-Ward” Progress in NDMM: New Developments With CD38 Antibody Quadruplets

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jun 3, 2024 28:41


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/PHX865. CME credit will be available until May 23, 2025.“Four-Ward” Progress in NDMM: New Developments With CD38 Antibody Quadruplets In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC., and Sanofi.Disclosure information is available at the beginning of the video presentation.

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast
Suzanne Lentzsch, MD, PhD / Joshua Richter, MD - “Four-Ward” Progress in NDMM: New Developments With CD38 Antibody Quadruplets

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Jun 3, 2024 28:34


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/PHX865. CME credit will be available until May 23, 2025.“Four-Ward” Progress in NDMM: New Developments With CD38 Antibody Quadruplets In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC., and Sanofi.Disclosure information is available at the beginning of the video presentation.

PeerView Internal Medicine CME/CNE/CPE Video Podcast
Suzanne Lentzsch, MD, PhD / Joshua Richter, MD - “Four-Ward” Progress in NDMM: New Developments With CD38 Antibody Quadruplets

PeerView Internal Medicine CME/CNE/CPE Video Podcast

Play Episode Listen Later Jun 3, 2024 28:34


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/PHX865. CME credit will be available until May 23, 2025.“Four-Ward” Progress in NDMM: New Developments With CD38 Antibody Quadruplets In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC., and Sanofi.Disclosure information is available at the beginning of the video presentation.

PeerView Internal Medicine CME/CNE/CPE Audio Podcast
Suzanne Lentzsch, MD, PhD / Joshua Richter, MD - “Four-Ward” Progress in NDMM: New Developments With CD38 Antibody Quadruplets

PeerView Internal Medicine CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jun 3, 2024 28:41


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/PHX865. CME credit will be available until May 23, 2025.“Four-Ward” Progress in NDMM: New Developments With CD38 Antibody Quadruplets In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC., and Sanofi.Disclosure information is available at the beginning of the video presentation.

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast
Suzanne Lentzsch, MD, PhD / Joshua Richter, MD - “Four-Ward” Progress in NDMM: New Developments With CD38 Antibody Quadruplets

PeerView Oncology & Hematology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Jun 3, 2024 28:41


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/PHX865. CME credit will be available until May 23, 2025.“Four-Ward” Progress in NDMM: New Developments With CD38 Antibody Quadruplets In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC., and Sanofi.Disclosure information is available at the beginning of the video presentation.

OncoAlert
The Hematology Round Up at #ASCO24

OncoAlert

Play Episode Listen Later Jun 3, 2024 7:10


Dear Colleagues,Welcome to this Hematology Round Up from hashtag#ASCO24 . WE have focused on Hematologic malignancies with 3 presentations which were presented on June 2nd, 2024The first presentation was the Phase 3 study results of isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) versus VRd for transplant-ineligible patients with newly diagnosed multiple myeloma (IMROZ) . Presented by Dr. FaconThis trial presentation came with a concomitant publication on the New England Journal of Medicine (NEJM).https://lnkd.in/d2dRh6HpThe Second Presentation was the Phase 3 randomized BENEFIT study of isatuximab (Isa) plus lenalidomide and dexamethasone (Rd) with bortezomib versus isard in patients with newly diagnosed transplant ineligible multiple myeloma (NDMM TI). Presented by Dr. LeleuThis trial presentation came with a concomitant publication on Nature Medicinehttps://lnkd.in/dSjVvk7XThe final presentation was Daratumumab (DARA) + bortezomib/lenalidomide/dexamethasone (VRd) in transplant-eligible (TE) patients (pts) with newly diagnosed multiple myeloma (NDMM): Analysis of minimal residual disease (MRD) in the PERSEUS trial. Presented by Dr Rodriguez-OteroDr. Landgren discussed how quadruple therapies showed higher rates of minimal residual disease (MRD) and longer progression-free survival compared to triplets, regardless of age and transplant eligibility, potentially making them a new standard of care for newly diagnosed Multiple Myeloma.He emphasized the importance of minimal residual disease as an endpoint in newly diagnosed multiple myeloma, suggesting that having it as an early endpoint for accelerated approval could give patients faster access to new therapies. However, he also highlighted that bortezomib increases the rate of peripheral neuropathy.Dr. Landgren pointed out that CD38 monoclonal antibodies narrow the gap between transplant-eligible, younger, and fit patients, and transplant-ineligible, older, and less fit patients with multiple myeloma.Thank you for your attention and enjoy ASCODisclosure: This Hematology Round Up was supported by Sanofi

PeerView Clinical Pharmacology CME/CNE/CPE Video
Suzanne Lentzsch, MD, PhD / Joshua Richter, MD - “Four-Ward” Progress in NDMM: New Developments With CD38 Antibody Quadruplets

PeerView Clinical Pharmacology CME/CNE/CPE Video

Play Episode Listen Later Jun 3, 2024 28:34


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME information, and to apply for credit, please visit us at PeerView.com/PHX865. CME credit will be available until May 23, 2025.“Four-Ward” Progress in NDMM: New Developments With CD38 Antibody Quadruplets In support of improving patient care, PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by educational grants from Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC., and Sanofi.Disclosure information is available at the beginning of the video presentation.

Pushing The Limits
Longevity Nexus: Where Science Meets Supplementation With Michael Antonelli

Pushing The Limits

Play Episode Listen Later May 30, 2024 49:36


The longevity research world is exploding right now, it's so exciting and the technology is advancing in leaps and bounds and we are able now to discover faster than ever before thanks to AI and co to test more molecules that can impact human health than ever before in the history of mankind. What would have taken years now takes weeks or months. In this episode I talk to Michael Antonelli CEO and founder of Healthgevity. Michael is a master formulator who has spent decades in the anti-ageing and longevity space learning at the feet of many masters and who is at the forefront of working with companies at the cutting edge in peptide and bioactive ingredient development. All his formulations are science backed with clinical research and I was excited to learn about something of these novel molecules Introduction to Healthgevity and its CEO, Michael Antonelli Overview of Healthgevity's approach: merging clinical research, AI, and medical expertise Exploring the importance of longevity in today's society Michael Antonelli's journey and motivation behind founding Healthgevity The role of cutting-edge science in developing longevity supplements How Healthgevity collaborates with clinical practitioners and doctors Deep dive into Healthgevity's science-backed formulations Examples of specific ingredients and their benefits in promoting longevity The impact of AI in optimizing formulations and personalizing supplementation Addressing common misconceptions about longevity supplements Future prospects and advancements in the longevity industry   BIO   Throughout a career spanning over 17 years, Michael passionately devoted himself to pioneering methods aimed at enhancing longevity, optimizing healthspan, and elevating overall quality of life. His focus revolves around collaborating with leading healthcare professionals, researchers, and other likeminded healthcare leaders to create natural solutions that elevate patient outcomes. Michael utilizes his past experiences that integrates a diverse range of therapies and services, spanning from precision diagnostics to practice management strategies, hormone optimization, nutritional supplements, and leveraging peptides. Previous roles included Chief Innovation Officer, Executive Director, and Business Development for leading companies within the healthcare industry before founding Healthgevity. His expertise extends beyond conventional approaches, emphasizing holistic well-being and personalized care as essential components to any successful medical practice. By championing novel methodologies and innovative technologies, Michal facilitates transformative changes within the healthcare landscape, fostering advancements that positively impact both practitioners and the individuals they serve.  Michael continues to remain dedicated to the pursuit of innovative strategies that enhance health and vitality while reshaping the paradigms of healthcare.   Some of the products mentioned in this podcast:   CARDIO NAD+ Vascular health and aging are the most important health care problem in the world today. Healthy aging requires healthy arteries and a healthy heart. Cardio NAD+ is a state-of-the-art solution which uses the most novel ingredients available to help optimize cardiovascular health. As one of the most important systems in your body, we have designed this combination to be synergistic to the many different areas of cardiovascular health while demonstrating cardioprotective effects including the emerging connection between NAD+ and heart health. Featured Supportive Benefits: Improves net NAD+ status by supporting both its synthesis and limiting its degradation Supports healthy blood pressure Improves vascular aging and endothelial function Supports healthy fibrinolytic activity and clotting function Promotes healthy circulation and blood flow Inhibits platelet & red blood cell aggregation Decreases blood viscosity Supports clinical measures of inflammation Supports healthy blood sugar and insulin levels Inhibits lipid peroxidation Supports healthy lipid metabolism Demonstrated reduction in various independent cardiovascular risk factors   Resolve+ Resolve+ contains numerous compounds that have been found to reduce the inflammatory response by targeting a variety of mechanisms.  Acmella oleracea ("jambu") is sourced from Sardinia, Italy and rich in alkylamides mainly represented by spilanthol. Its flowers are widely used in folk medicine to treat toothache due to tingling, numbness, and local anesthesia caused in the mouth.  Acmella oleracea has been shown to be active in fatty acid amide hydrolase (FAAH) inhibition the enzyme responsible for the degradation of fatty acid amides and cannabinoid type 2 (CB2) activation.  There are almost 100 studies suggesting the supportive potential for anti-inflammatory, antioxidant, and analgesic effects of Acmella. Studies reported in this review confirmed activities of Acmella, postulating that transcription factors of the nuclear factor-κB family (NF-κB) trigger the transcription iNOS and COX-2 and several other pro-inflammatory mediators, such as IL-6, IL-1β, and TNF-α. Curcumin, a natural polyphenolic compound derived from turmeric (Curcuma longa L.), has been well documented to exhibit various health benefits. There have been many claims on the health benefits of curcumin on neurological, cardiovascular, lung, metabolic, and liver function, mainly through its anti-inflammatory and antioxidant properties. Despite its promising potential, the clinical application of curcumin has been limited due to its low bioavailability. To enhance curcumin absorption, we are the first to feature Theracurmin Super® 85X, a proprietary curcumin utilizing the latest technology that transforms standard curcumin into an amorphous structure. Theracurmin Super® 85X uses the latest technology to transform regular curcumin particles into a more bioavailable structure. This is done by splitting curcumin particles' crystal structure amorphous, therefore, making it easily absorbed and bioavailable to maximize its supportive potential. Tetrahydrocurcumin (4-HC) is the key bioactive derivative of curcumin, it's also given credibility as the engine behind all that curcumin brings to the table. With a newfound ability to extract and isolate the compound, research has even seen tetrahydrocurcumin outperform its parent compound in several tests of its capabilities. Researchers have also confirmed that 4-HC attenuated pro-inflammatory indicators like interleukin-1, interleukin-6, TNF-⍺, and prostaglandin E2.  After reviewing the data, we found many advantages to infuse tetrahydrocurcumin as CurcuPrime® stacked with Theracurmin Super® 85X into Resolve+. Quercetin is a well-known studied dietary flavonoid ubiquitously present in various vegetables. Quercetin is known for its antioxidant activity in radical scavenging and anti-allergic properties characterized by stimulation of immune system, antiviral activity, inhibition of histamine release, decrease in pro-inflammatory cytokines, leukotrienes creation, and suppresses interleukin IL-4 production.  Multiple studies have confirmed its supportive potential as an immune modulator and its ability to support a healthy inflammatory response. It can improve the Th1/Th2 balance, and restrain antigen specific IgE antibody formation However, chemical instability, poor water solubility and low bioavailability of quercetin greatly limit its applications which is why a phytosome technology which we feature in resolve is the preferred delivery system to overcome these limitations.  This enhanced form of quercetin has been shown to be as much as 20 times better absorbed than other quercetin options.  Casperome®  boswellia phytosome is a potent extract made from the resin of Boswellia serrata trees and is also referred as Indian frankincense. Boswellia extracts have been demonstrated to be effective in the management of various inflammatory response functions including those that occur in the bowel, joints, bones, respiratory airways and in the brain. The mechanism of action that involves the modulation of the natural inflammatory response both acting on prostanoid synthesis (mPGE2S) and protein degradation (caspases), and transcription factors (Nf-κB).  We have selected Casperome® which is a highly standardized in boswellic acids to match the natural composition of boswellia, formulated with phytosome technology to achieve optimized absorption and has been validated by over 10 human studies. Perilla frutescens is an annual herb belonging to the mint family (Lamiaceae). It is mainly produced in countries like China, Japan, India, Thailand and Korea. Recently, Perilla is gaining more attention because of its medicinal benefits and phytochemical contents. The functional compounds of Perilla Seed Extract are flavonoid Aglycons – polyphenols such as Luteolin, Apigenin, Chrysoeriol, and Rosemarinic Acid. Studies have shown that Perilla seed polyphenols regulate allergic and inflammatory response due to its 5-lipoxygenase inhibitory activity and suppression potential of histamine release from mast cells. AstraGin® is a natural compound derived from the roots of two traditional Chinese herbs: Panax notoginseng and Astragalus membranaceous which contain astragaloside I, II, IV and ginsenoside Rb1. AstraGin® has been shown to provide full-spectrum gut support through enhanced absorption, microbiota and immune cell viability, and supporting a health. AstraGin® has been shown in numerous studies to increase the absorption of peptides, amino acids, fatty acids, vitamins, and phytonutrients by up regulating the absorption specific mRNA and transporters, such as SGLT1, CAT1, and GLUT4. Additionally, AstraGin® was shown to reduce intestinal inflammatory biomarker MPO, the pro-inflammatory cytokines IL-6, IL-17, and IL-1β in ulcerative colitis patients. Prime Gut Health Prime Gut Health was created because the digestive system is the foundation of getting and staying healthy. There are many benefits to an optimal digestive system such as a healthy immune system and the protection against harmful viruses, bacteria, fungi, and yeast. The ingredients selected in Prime Gut Health work together to help restore gut homeostasis and GI barrier function.    There are many benefits to taking Prime Gut Health, including:  Supports healthy GI barrier function*   Helps restore gut homeostasis* Binds and neutralizes bacterial toxins in the gut*  Promotes a healthy immune system and respiratory health* Supports digestive health and gut discomfort*  Increased nutrient absorption*  Supports gut inflammation especially within the intestinal wall*  Promotes a healthier GI environment* Promoted regularity and healthy bowel function*    WHAT MAKES PRIME GUT HEALTH SO IMPACTFUL? ImmunoLin® is the branded ingredient serum-derived bovine immunoglobulin/protein isolate (SBI) with over 40 human studies demonstrating its clinical efficacy in digestive and immune health.   SBI has been shown to be a broad-spectrum modulator of the immune system by targeting excessive or imbalanced immunity.* In addition, ImmunoLin® works by binding, neutralizing, and removing pathogenic bacteria, viruses, and other gut irritants that can lead to inflammation.* It also helps to repair the gut lining and restore gut homeostasis.*   Tributyrin (as CoreBiome®) is a postbiotic and the most important short-chain fatty acid (SCFA) for supporting digestive, gut, immune and gastrointestinal health. CoreBiome® is a unique butyrate formula intended to pass intact through the stomach and small intestine to deliver butyrate right where it's needed—the colon.  CoreBiome® supports: Delivery of butyrate to the colon where it helps maintain the integrity of your intestinal lining* Helps repair the gut lining and restore gut homeostasis*  Tight junctures in the intestinal lining*  Regularity and regulation of a normal inflammatory response* Sporebiotics:  Soil-based probiotics have been touted for their stability, ability to improve digestion, stimulate the immune system, and help maintain a healthy gut microbiota. Bacillus coagulans SNZ 1969®, Bacillus subtilis SNZ 1972 and Bacillus clausii SNZ 1971 are supported with an over 50 year history of use and over 30 human studies covering gut health, gastrointestinal discomfort, immunity against GI tract pathogens, inhibition of food borne pathogens, inhibition of bacteria causing dental carries and gingivitis along with bacterial vaginosis. AstraGin® is a 100% natural compound derived from the roots of two traditional Chinese herbs: Panax notoginseng and Astragalus membranaceous,  containing astragaloside I, II, IV and ginsenoside Rb1. AstraGin® enhances nutrient absorption by up-regulating nutrient transporters, such as CAT1, SGLT1, and FR. AstraGin® restores gut wall integrity by triggering an anti-inflammatory response and activating the mTOR pathway for rapid intestinal stem cell migration and differentiation in the inflamed intestinal mucosal barrier (epithelial cell and tight junction). AstraGin® promotes gut ecosystem homeostasis by the symbiotic effect of restoring gut wall integrity and increasing microbiota-immunity communication.  AstraGin® activates the immune system through the symbiotic effect of improved gut wall integrity and enhanced microbiota-immunity communication. AstraGin® demonstrated in a recent published human clinical trial, to improve upon a number of measurable factors relating to gut health making it an ideal addition into Prime Gut Health.  PrimeTime  Prime Time is a comprehensive blend of 12 key natural ingredients shown to have a role in supporting age management powered by industry leading 10mg's of spermidine per serving.  Prime Time has been formulated with ingredients to mimic fasting and catalyze your body's natural ability to rid itself of aged cells.  Various publications demonstrate the potential this formula will have in your longevity protocols as Prime Time was formulated to support:   Epigenetic aging*  Boosting autophagy and promote cellular renewal*  Fasting* Memory, cognition, and brain health* Cardiovascular health* Beauty from within* Mitochondria*  WHAT MAKES PRIME TIME SO IMPACTFUL? Spermidine Spermidine, a natural polyamine, plays a critical role in molecular and cellular interactions involved in various physiological and functional processes. Spermidine has been shown to modulate aging, suppress the occurrence and severity of age-related diseases, and prolong lifespan.  The concentration of spermidine declines with age, and exogenous spermidine supplementation reverses age- associated adverse changes and supports health span. Given that it interacts with various molecules, spermidine influences aging through diverse mechanisms.  Autophagy is the body's way of cleaning out damaged cells, to regenerate newer, healthier cells and is the main mechanism of spermidine. In addition, spermidine exerts its effects through other mechanisms, including anti-inflammation, histone acetylation reduction, lipid metabolism and regulation of cell growth and signaling pathways. Nicotinamide mononucleotide  Nicotinamide mononucleotide, a naturally occurring molecule present in all species.  NMN is rapidly absorbed and converted to NAD+, which evidence shows declines as we age.  In numerous studies, supplementation has increased NAD+ biosynthesis, suppressed age-related adipose tissue inflammation, enhanced insulin secretion and insulin action, improved mitochondrial function, and improves neuronal function in the brain among much more. Epigallocatechin-3-gallate (EGCG)  Epigallocatechin-3-gallate (EGCG) is the major catechin in green tea.  There is consistency in the literature about the beneficial role of green tea on senescence-related mechanisms, thanks to its scavenging properties against reactive oxygen species (ROS) and reactive nitrogen species (RNS) and its ability to stimulate autophagy  Alpha-ketoglutarate (AKG) Alpha-ketoglutarate (AKG) is a molecule involved in several metabolic and cellular pathways that declines with age. It works as an energy donor, a precursor in amino acid production, and a cellular signaling molecule, and it is a regulator of epigenetic processes.  Dihydroquercetin (Taxifolin)  Dihydroquercetin is a powerful antioxidant of plant origin that can protect cells from the harmful effects of free radicals and protect cell membranes against damage Apigenin Apigenin is a natural bioactive plant polyphenol with antioxidant, anti-inflammatory and immune system boosting properties.  It also helps to support against oxidative stress for better cellular function. Studies have shown that apigenin prevents excessive loss of NAD+ by reducing the amount of circulating CD38, allowing NAD+ stores to remain at higher, more youthful levels. Luteolin Luteolin is a flavonoid naturally found in plants. Flavonoids like luteolin have been found to have beneficial effects on human health by reducing oxidative stress.   Trimethylglycine (TMG) Trimethylglycine (TMG) is an amino acid derivative that occurs in plants and has been shown to support methylation which, in turn, supports the homocysteine levels. Taking TMG along with NMN provides the ideal balance for NAD+ production in the body.  Resveratrol  Resveratrol is part of a group of compounds called polyphenols, which act as antioxidants to protect the body against age-related conditions.The anti-aging mechanisms of resveratrol are mainly modulating oxidative stress, relieving inflammatory reaction, improving mitochondrial function, and regulating apoptosis. Resveratrol is considered for the prevention and support of aging and age-related diseases as it mimics the effects of calorie restriction.  Pterostilbene Pterostilbene is a phenolic compound in the same family as resveratrol and is present in small amounts in a large variety of foods and beverages like blueberries or red wine. Multiple studies confirm pterostilbene's remarkable anti-aging effects. Cell and animal studies have shown that pterostilbene can extend the lifespan of various animal models of human longevity by regulating three major pathways linked to longevity: mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), and sirtuins Bergamot Bergamot (Citrus bergamia) is a type of citrus fruit native to Italy. It has been shown that bergamot juice exerts antioxidant, cardioprotective properties and antisenescence effects.  AstraGin®  AstraGin® is a natural compound derived from the roots of two traditional Chinese herbs: Panax notoginseng and Astragalus membranaceous. AstraGin® increases the absorption of peptides, amino acids, fatty acids, vitamins, and phytonutrients by up-regulating absorption-specific m RNA and transporters such as SGLT1, CAT1, and GLUT4. Check out all the healthgevity products in our shop.    Personalised Health Optimisation Consulting with Lisa Tamati Lisa offers solution focused coaching sessions to help you find the right answers to your challenges. Topics Lisa can help with:  Lisa is a Genetics Practitioner, Health Optimisation Coach, High Performance and Mindset Coach. She is a qualified Ph360 Epigenetics coach and a clinician with The DNA Company and has done years of research into brain rehabilitation, neurodegenerative diseases and biohacking. She has extensive knowledge on such therapies as hyperbaric oxygen,  intravenous vitamin C, sports performance, functional genomics, Thyroid, Hormones, Cancer and much more. She can assist with all functional medicine testing. Testing Options Comprehensive Thyroid testing DUTCH Hormone testing Adrenal Testing Organic Acid Testing Microbiome Testing Cell Blueprint Testing Epigenetics Testing DNA testing Basic Blood Test analysis Heavy Metals  Nutristat Omega 3 to 6 status and more  Lisa and her functional medicine colleagues in the practice can help you navigate the confusing world of health and medicine . She can also advise on the latest research and where to get help if mainstream medicine hasn't got the answers you are searching for whatever the  challenge you are facing from cancer to gut issues, from depression and anxiety, weight loss issues, from head injuries to burn out to hormone optimisation to the latest in longevity science. Book your consultation with Lisa    Join our Patron program and support the show Pushing the Limits' has been free to air for over 8 years. Providing leading edge information to anyone who needs it. But we need help on our mission.  Please join our patron community and get exclusive member benefits (more to roll out later this year) and support this educational platform for the price of a coffee or two You can join by going to  Lisa's Patron Community Or if you just want to support Lisa with a "coffee" go to  https://www.buymeacoffee.com/LisaT to donate $3   Lisa's Anti-Aging and Longevity Supplements  Lisa has spent years curating a very specialized range of exclusive longevity, health optimizing supplements from leading scientists, researchers and companies all around the world.  This is an unprecedented collection. The stuff Lisa wanted for her family but couldn't get in NZ that's what it's in her range. Lisa is constantly researching and interviewing the top scientists and researchers in the world to get you the best cutting edge supplements to optimize your life.   Subscribe to our popular Youtube channel  with over 600 videos, millions of views, a number of full length documentaries, and much more. You don't want to miss out on all the great content on our Lisa's youtube channel. Youtube   Order Lisa's Books Lisa has published 5 books: Running Hot, Running to Extremes, Relentless, What your oncologist isn't telling you and her latest "Thriving on the Edge"  Check them all out at  https://shop.lisatamati.com/collections/books   Perfect Amino Supplement by Dr David Minkoff Introducing PerfectAmino PerfectAmino is an amino acid supplement that is 99% utilized by the body to make protein. PerfectAmino is 3-6x the protein of other sources with almost no calories. 100% vegan and non-GMO. The coated PerfectAmino tablets are a slightly different shape and have a natural, non-GMO, certified organic vegan coating on them so they will glide down your throat easily. Fully absorbed within 20-30 minutes! No other form of protein comes close to PerfectAminos Listen to the episode with Dr Minkoff here:    Use code "tamati" at checkout to get a 10% discount on any of their devices.   Red Light Therapy: Lisa is a huge fan of Red Light Therapy and runs a Hyperbaric and Red Light Therapy clinic. If you are wanting to get the best products try Flexbeam: A wearable Red Light Device https://recharge.health/product/flexbeam-aff/?ref=A9svb6YLz79r38   Or Try Vielights' advanced Photobiomodulation Devices Vielight brain photobiomodulation devices combine electrical engineering and neuroscience. To find out more about photobiomodulation, current studies underway and already completed and for the devices mentioned in this video go to www.vielight.com and use code “tamati” to get 10% off     Enjoyed This Podcast? If you did, subscribe and share it with your friends! If you enjoyed tuning in, then leave us a review and share this with your family and friends. Have any questions? You can contact my team through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts.  To pushing the limits, Lisa and team

ASCO Daily News
Novel Approaches in Hematologic Malignancies at ASCO24

ASCO Daily News

Play Episode Listen Later May 24, 2024 22:33


Dr. John Sweetenham and Dr. Marc Braunstein look ahead at key abstracts across the spectrum of hematologic malignancies that will be presented at the 2024 ASCO Annual Meeting, including the OPTIC trial in chronic myeloid leukemia, treatment options for transplant-ineligible patients with multiple myeloma, and the 7-year analysis of the ECHELON-1 trial in classical Hodgkin lymphoma. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham from UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and the host of the ASCO Daily News Podcast. I'm delighted to be joined again this year by Dr. Marc Braunstein, a hematologist and oncologist at the NYU Perlmutter Cancer Center in New York. We're going to be discussing some of the key abstracts in hematologic malignancies that will be featured at the 2024 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode, and disclosures of all guests on the podcast are available at asco.org/DNpod.  Marc, it's great to have you back on the podcast. Dr. Marc Braunstein: It's a pleasure to be back, John.  Dr. John Sweetenham: There are some exciting abstracts to be presented at this year's meeting, and I would like to begin, if we can, with Abstract 6501. As you know, this reports the four-year results from the OPTIC trial of ponatinib in patients with chronic-phase CML and the T315I mutation. Can you tell us about the trial and about these latest follow-up results? Dr. Marc Braunstein: Sure. Well, we've made tremendous progress in managing patients with CML in the past two decades using these oral tyrosine kinase inhibitors such as ponatinib. Ponatinib is a third-generation TKI that has activity in both Philadelphia-positive ALL as well as CML, and can overcome the resistance mutation you mentioned, called the T315I mutation, which is sometimes found following prior TKI therapy. The OPTIC study is a multicenter phase 2 randomized study of various doses of ponatinib in 283 chronic phase CML patients who had received 2 or more prior lines of therapy or those who had the presence of a T315I mutation, with the current analysis examining the major remission at 48 months, PFS, as well as OS. Of note, in this study, after patients have achieved a major remission with a transcript level of 1% or less, the study allowed for dose reduction of ponatinib from the original dose of either 45 milligrams or 30 milligrams to a reduced dose of 15 milligrams.  So, when we look at the results, we find that the patients who had the highest overall response rates and higher rates of molecular remission were those who received the 45-milligram dose. And remember, these patients were allowed to be dose-reduced to the 15-milligram dose once they achieved a molecular remission of 1% or less. In addition, the rates of overall survival were highest in the 45-milligram dose as well. When looking at the T315I subgroup, the rates of molecular remission, the depth of remission, and the rates of progression-free survival, in general, were lower in that subgroup, but still higher in the 45-milligram dose than the 35- milligram dose.  Furthermore, when looking at the rates of treatment-emergent adverse events leading to discontinuation, they were 8% in the 45-milligram dose compared to 14% in the 30-milligram dose and 5% in the patients who only received the 15-milligram dose. The authors have concluded that the 45-milligram dose, with the potential to be reduced to 15 milligrams after achieving 1% or less of the BCR-ABL transcript level, seems to be the right balance between efficacy and safety.  Dr. John Sweetenham: Thanks, Marc. In the longer term, do you think that this study will, in any way, affect the position of ponatinib in the treatment algorithm for CML? Is it going to remain as a second or third-line option, or do you think there's any chance it will be moved up? Dr. Marc Braunstein: Well, that's a great question. There are other TKIs, such as asciminib, that also target the T315I mutation, and that mutation tends to develop after prior first-line or second-line TKI therapy. But given its activity in both ALL and CML, I think it's certainly reasonable to expect that ponatinib will be used in earlier lines of therapy given its efficacy in later lines. Dr. John Sweetenham: Let's change gears and move the focus to acute myeloid leukemia. There has been a lot of discussion around frailty in many different malignancies, but the impact of frailty on outcomes in AML is maybe something that hasn't been quite so well studied. In Abstract 6506, investigators did a population-based study in Ontario, Canada, that assessed the patient's frailty risk and the impact that might have on outcomes. What are your takeaways from this study, and how do you think these data will help optimize treatment decisions?  Dr. Marc Braunstein: Yeah, I'm glad we're talking about this abstract John, because frailty scores are increasingly being used in hematologic malignancies to help guide goals and intensity of care. And as opposed to using age or performance status alone, these composite frailty assessment tools, such as the MFI tool that they used in this particular study, take into account multiple variables that are both physiologic, such as the patient's comorbidities, as well as social, and what kind of support system do they have, and things of that nature. And that accounts for their overall fitness. So, in this retrospective cohort study that was a population-based study in Ontario between 2006 and 2021, they looked at 5,450 patients retrospectively with acute leukemia and grouped those patients into 3 categories based on this frailty index. Patients who are either fit, somewhere in the middle between fit or frail, which they call pre-frail, or frail. And they looked at outcomes such as overall survival, comparing patients who got intensive chemotherapy regimens for induction or those who got non-intensive therapy for induction. Patients in either group could have been assigned to either fit, pre-frail, or frail although there are much more fit patients than those who got intensive induction.  And so, looking at their findings, it was noted that patients who were in the frail category, not entirely unexpectedly, had lower overall survival when compared to those who were fit or pre-frail. I think the value of a study like this is not just to highlight the benefit of frailty scores to help predict which patients may ultimately have a shorter survival, but also to help potentially guide which patients may be more suitable for intensive versus less intensive induction. I will note that this study was conducted in an era where we didn't have the same sorts of less intensive induction that are very effective in less fit patients, such as the combination of azacytidine and venetoclax, which is commonly used in less fit patients nowadays. So, the study may encompass patients who didn't have access to that therapy because it wasn't available during that time. But I think it still, overall, does highlight the fact that assessing fitness or frailty in acute myeloid leukemia is important for predictive value. Dr. John Sweetenham: I agree. Marc, I don't know what your thoughts are on this, but it goes either way. I mean, I think that, if I remember the numbers correctly, 25% of fit patients received non-intensive therapy. So, is there a missed opportunity there for that group of patients who actually may have tolerated the intensive therapy but it was never offered? Dr. Marc Braunstein: That's an excellent point, John, and I think that highlights the importance of frailty indices because they take into account much more than one particular factor, or even just a subjective assessment of the patient in real time when they're first presenting. And they may have disease-specific features that are decreasing, say one element of their assessment such as their performance status. So, really taking these composite fitness scores into account may actually allow you to escalate therapy in a patient who may actually be fit but maybe perceived as less fit when they present. Dr. John Sweetenham: Yeah. So, I think, as you mentioned, there are better treatment options out there now maybe than there were at the time this study was conducted. Nevertheless, there may still be that opportunity for more intensive therapy for some of these patients when they are more holistically assessed.  Let's move on and switch gears once again and talk about a study in multiple myeloma, the so-called IMROZ study, which is Abstract 7500. So, this is a study looking at treatment options for transplant-ineligible patients with newly diagnosed multiple myeloma. Some of these patients may not have a chance for subsequent therapy if they are not eligible for transplant. What are your thoughts on this study? Do you think we're closer to a new standard of care for patients who are not going to proceed to an autologous stem cell transplant?  Dr. Marc Braunstein: It seems like every year there's a new standard of care for newly diagnosed multiple myeloma because there's so much data emerging, which is just wonderful. So, I think as background, at the 2023 ASH meeting, the IsKia study was presented, which is a randomized phase 3 study in newly diagnosed transplant-eligible patients. And that was using isatuximab with carfilzomib, lenalidomide, and dexamethasone upfront and that study did show a benefit in terms of reducing minimal residual disease compared to carfilzomib, lenalidomide, and dexamethasone alone. But that study was looking at fit newly diagnosed patients who were going on to stem cell transplant. Right now, the standard of care for patients who are not eligible for transplant is generally to use a 2 or 3-drug regimen, such as daratumumab, lenalidomide, and dexamethasone, based on the phase 3 MAYA study. But this study is really unique in that it looks at using a quadruplet regimen in patients who are transplant ineligible or not intended to go for transplant.  So, the phase 3 IMROZ study was a randomized study of 446 patients that compared isatuximab, bortezomib, lenalidomide, and dexamethasone to bortezomib, lenalidomide, and dexamethasone alone. So, a quad versus a triplet regimen. The primary endpoint in this study was progression-free survival, but they also looked at secondary endpoints, such as complete response rate and minimal residual disease negativity.   Just to quickly highlight the results and then discuss the standard of care, the median duration of treatment in this study was 53 months in the quad regimen and 31 months in the control arm. At a median follow-up of about 60 months, the progression-free survival was not reached with the quad regimen versus 54 months in the triplet, and that was a significant difference. In addition, the safety profile was pretty much consistent with the class, there were a bit more grade three or higher treatment-emergent adverse events with the ESA-containing regimen, 92% versus 84%, but no difference in adverse events leading to discontinuation in either arm.   So, this study is certainly compelling in terms of using quadruplet-based regimens that contain an anti-CD38 monoclonal antibody for newly diagnosed patients who are not intended to undergo transplant. I think at the meeting, I will be interested to see the patient population that was included. Patients who are over the age of 80, for example, are excluded. So, I would like to know more about their fitness level and performance status. But I think it's clear, John, that using quad regimens over triplet regimens is just consistently superior in terms of efficacy outcomes. Dr. John Sweetenham: Right. I guess that, even though maybe we can't focus on the specific agents right now, it looks as if quad regimens are going to be the standard of care regimens for the future in this group. Do you think that is fair?  Dr. Marc Braunstein: Very likely. Dr. John Sweetenham: Absolutely. Well, that's a pretty challenging group of patients.   And so to move on again, let's talk about another, perhaps equally challenging group - patients with mantle cell lymphoma, particularly those who carry certain mutations. The so-called SYMPATICO study, which is reported in Abstract 7007, presents data on the efficacy and safety of ibrutinib and venetoclax in patients with mantle cell lymphoma who carry a TP53 mutation. We know that this mutation confers a high risk of early progressive disease and poorer outcomes when these patients are treated with standard chemoimmunotherapy for mantle cell. Trials to date have been limited to small single-arm studies. Can you tell us a little bit about this study and the outcomes and what you think it means for the future?  Dr. Marc Braunstein: As a background, although BTK inhibitors such as ibrutinib have yet to be approved for newly diagnosed mantle cell lymphoma, acalabrutinib and zanubrutinib, which are second-generation BTK inhibitors, are FDA-approved for previously treated mantle cell lymphoma. Ibrutinib was withdrawn from the market. The lead author of this abstract, Dr. Michael Wang, had presented a late-breaking data from the phase 3 SYMPATICO trial at ASH last year, in which 267 patients with relapsed or refractory mantle cell lymphoma after one to five prior lines of therapy were randomized to receive the combination of ibrutinib plus the BCL-2 inhibitor venetoclax or ibrutinib plus placebo. That study showed there was a 32 versus 22-month progression-free survival with a hazard ratio of 0.65 at a median follow-up of 51 months, indicating the PFS benefit of the combination of ibrutinib and venetoclax compared to ibrutinib with placebo.   So that leads us to this subgroup analysis in the current study being presented at ASCO, in which they looked at a subgroup of patients with mantle cell lymphoma who are at very high risk for treatment failure and early relapse - those are patients who have a mutation in TP53, which again is high risk for treatment failure. This abstract examined an open-label cohort of 44 first-line patients, as well as 75 patients who were in the relapse/refractory cohort, and compared to patients who either did or did not have the P53 mutation. When we look at the progression-free survival outcomes, the median progression-free survival in the first-line cohort of patients who did not have a P53 mutation was not reached, whereas those with the P53 mutation had a median progression-free survival of 22 months, which is still meaningful but still less than those who did not have a P53 mutation. Which again is not entirely unexpected. But the overall response rate of the combination of ibrutinib and venetoclax was very high at 90%, and the median duration of response was about 21 months.  Now comparing this to the relapse/refractory cohort, in those without a P53 mutation, the progression-free survival of the combination of ibrutinib and venetoclax was about 47 months versus those who don't have the P53 mutation was about 21 months with an overall response rate of 80%. I think one takeaway looking at this comparison of the first-line and relapse/refractory setting is that patients seem to do very similar in terms of overall response rate and progression-free survival, whether they were in the first line or in the later lines of treatment if they had the P53 mutation, which says that the combination of ibrutinib and venetoclax is effective no matter which phase of the disease the patient might be in, indicating its overall activity and being strong.    Dr. John Sweetenham: Yeah, I thought that was an interesting observation, actually, how similar the outcomes were in those two groups.  Dr. Marc Braunstein: No, I agree. And I think although patients with TP53 mutations did comparatively worse than those without the mutation according to progression-free survival, overall response rate, or complete remission rates, they did seem to be similar whether a patient was in first-line or relapsed refractory if they were P53 mutant and were treated with this combination. So, I think we need further data in the first line, such as the data that's awaiting publication from the TRIANGLE study, which is examining upfront ibrutinib. But certainly, BTK inhibitors have significant activity in either the first line or the relapse setting of mantle cell lymphoma.  Dr. John Sweetenham: Great. Thanks, Marc.  Let's wind up with one more abstract, and this is Abstract 7053. It's a 7-year analysis of the so-called ECHELON-1 study. This was a study comparing the standard of care, ABVD, with the same regimen with bleomycin substituted by brentuximab vedotin for patients with previously untreated advanced-stage classical Hodgkin lymphoma. The study at the time it was originally reported, resulted in a significant practice change in the first-line therapy of Hodgkin's lymphoma. We now have mature follow-up. What are your take-homes from this study? Dr. Marc Braunstein: The ECHELON-1 study has certainly been a practice-changing clinical trial where, as you said, brentuximab with the backbone of AVD was compared to ABVD, which was the prior standard. And this was examined in newly diagnosed patients with classical Hodgkin lymphoma who were at advanced-stage, stage 3 or 4. The publication, first of the progression-free survival, and more recently, in the New England Journal of Medicine in 2022, where we saw the 6-year overall survival was 94% with the brentuximab-containing arm versus 89% in the control arm, established the brentuximab AVD, or otherwise called AAVD, as the standard of care in advanced stage newly diagnosed classical Hodgkin lymphoma. The current study is now reporting 7-year follow-up on about 1,300 randomized patients who were enrolled in this impressive study.   Though at a median follow-up of 89 months now, the 7-year overall survival was quite similar, 94% versus 89%, again favoring the brentuximab-containing arm. In particular, this was driven by patients who had stage 4 disease or those patients who were aged less than 60 in subgroup analyses. So, what I take away from this abstract in the 7-year follow-up of the ECHELON-1 is that brentuximab with AVD remains the standard of care for previously untreated advanced-stage classical Hodgkin lymphoma. It is worth noting that the SWOG S1826 study that was presented at ASCO last year compared nivolumab with AVD compared to brentuximab AVD and did show a slight PFS advantage of 94% versus 86% with nivolumab AVD. Obviously, these were different studies with different patient populations enrolled, so we're really just cross-comparing different studies. But I think brentuximab AVD, given the survival benefit that is retained now at seven years in the current abstract, still remains the standard of care for advanced-stage classical Hodgkin lymphoma. The role of immune checkpoint inhibitors like nivolumab is making headway in terms of treating newly diagnosed patients as well. Dr. John Sweetenham: Yeah, thanks, Marc. I mean, one of the observations that I thought was of interest in this study was the outcome for patients who were PET-2 positive, when you compare AAVD and ABVD. It does seem as if even in those patients who are PET-2 positive, having had AAVD, they still apparently have a better outcome than those who received ABVD in that situation who were PET-2 positive. So, I think that's another interesting observation. I'm not quite sure what it means, except speaking to the overall superior efficacy of that regimen. Dr. Marc Braunstein: You make a great point, John, because it's worth noting that in ECHELON-1, a PET scan was done after cycle 2, but the study was not PET-adapted. So even if you had a positive PET, you continued for the full six cycles of treatment. But PET-2 status is often used in various studies of Hodgkin lymphoma to guide whether to give additional cycles or escalate therapy. So, I think the benefit of presenting those subgroups is that even if you were PET-2 positive, you still did better by continuing on the brentuximab-containing regimen. Dr. John Sweetenham: Yeah, exactly. I mean, the other important takeaway message, I think, is that the outcome for patients with advanced Hodgkin lymphoma seems to continue to steadily improve, which is great news and also really remarkable. And I'm excited to see there may be some additional data presented at one of the late-breaking abstracts in this year's meeting, so it will truly be interesting to see what that shows us as well.  Dr. Marc Braunstein: Incredible. Dr. John Sweetenham: Well, Marc, as always, thank you for sharing your insights with us today on the ASCO Daily News Podcast. We look forward very much to hearing the updated data from these abstracts at the meeting.  Dr. Marc Braunstein: As do I and thank you so much for inviting me again.  Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Find out more about today's guest: Dr. Marc Braunstein @docbraunstein   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Facebook  ASCO on LinkedIn    Disclosures:  Dr. John Sweetenham: Consulting or Advisory Role: EMA Wellness   Dr. Marc Braunstein: Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb/Celgene, Adaptive Biotechnologies, GlaxoSmithKline, ADC Therapeutics, Janssen Oncology, Abbvie, Guidepoint Global, Epizyme, Sanofi, CTI BioPharma Corp Speakers' Bureau: Janssen Oncology Research Funding (Institution): Janssen, Celgene/BMS

Pushing The Limits
NAD Metabolism For Longevity With Professor Joseph Baur

Pushing The Limits

Play Episode Listen Later May 16, 2024 87:24


Ever since the book "Lifespan" came out from Dr David Sinclair, everyone and their dog and has been supplementing with nicotinamide mononucleotide and nicotinamide riboside and an effort to increase our levels in the body.NAD is essential to life. No energy production can happen without NAD. NAD Also decreases as we age so the question has always been should we and can we increase our NAD levels. As usual in biology it's very complicated and as the science has developed we have learned many new detailed insights.  Here is an update on the latest in that science. In this episode of "Pushing The Limits" I have the wonderful privilege of interviewing one of the world's leading researchers in NAD metabolism, sirtuin genes and metabolic health Professor Joseph Baur. Professor at the Perelman School of Medicine of the University of Pennsylvania, How can you increase NAD+ levels? And do higher NAD+ levels really lead to better metabolic health? What does the research say on their benefits for Longevity. We cover this critical pathway in-depth looking what the research is saying and what it currently isn't and what we have still to learn. We look into mice studies and then also where the human research is at. We cover the salvage pathway as well as the Preiss Handler pathway. The possible role of the Microbiome and in NAD metabolism. We also discussed the various NAD pools and why the mitochondria maybe a key in a NAD pool. We discuss the transporter for NAD into the mitochondria that was recently discovered by Prof Baur and other labs. We discuss also the possible risk factors and how we can mitigate these. We look at where the research is at in relation to cancer and NAD Metabolism. The role of CD 38 as a voracious consumer of in NAD and how lowering CD38 in the body may be even more beneficial than taking the precursor enzymes. We discuss also why CD38 increases as we age and what we can do about it and the role of senolytics. How we can increase the NAMPT enzyme so we recycle more of our NAD And whether we need to support our methylation donors when we are supplementing with the likes of NMB and NR.   If you are fascinated by longevity science and want to know how you can optimise your health moving forward then this is the episode for you! Want to try NMN, TMG and quercetin to support your healthy NAD metabolism you can find them in my shop   Personalised Health Optimisation Consulting with Lisa Tamati Lisa offers solution focused coaching sessions to help you find the right answers to your challenges. Topics Lisa can help with:  Lisa is a Genetics Practitioner, Health Optimisation Coach, High Performance and Mindset Coach. She is a qualified Ph360 Epigenetics coach and a clinician with The DNA Company and has done years of research into brain rehabilitation, neurodegenerative diseases and biohacking. She has extensive knowledge on such therapies as hyperbaric oxygen,  intravenous vitamin C, sports performance, functional genomics, Thyroid, Hormones, Cancer and much more. She can assist with all functional medicine testing. Testing Options Comprehensive Thyroid testing DUTCH Hormone testing Adrenal Testing Organic Acid Testing Microbiome Testing Cell Blueprint Testing Epigenetics Testing DNA testing Basic Blood Test analysis Heavy Metals  Nutristat Omega 3 to 6 status and more  Lisa and her functional medicine colleagues in the practice can help you navigate the confusing world of health and medicine . She can also advise on the latest research and where to get help if mainstream medicine hasn't got the answers you are searching for whatever the  challenge you are facing from cancer to gut issues, from depression and anxiety, weight loss issues, from head injuries to burn out to hormone optimisation to the latest in longevity science. Book your consultation with Lisa    Join our Patron program and support the show Pushing the Limits' has been free to air for over 8 years. Providing leading edge information to anyone who needs it. But we need help on our mission.  Please join our patron community and get exclusive member benefits (more to roll out later this year) and support this educational platform for the price of a coffee or two You can join by going to  Lisa's Patron Community Or if you just want to support Lisa with a "coffee" go to  https://www.buymeacoffee.com/LisaT to donate $3   Lisa's Anti-Aging and Longevity Supplements  Lisa has spent years curating a very specialized range of exclusive longevity, health optimizing supplements from leading scientists, researchers and companies all around the world.  This is an unprecedented collection. The stuff Lisa wanted for her family but couldn't get in NZ that's what it's in her range. Lisa is constantly researching and interviewing the top scientists and researchers in the world to get you the best cutting edge supplements to optimize your life.   Subscribe to our popular Youtube channel  with over 600 videos, millions of views, a number of full length documentaries, and much more. You don't want to miss out on all the great content on our Lisa's youtube channel. Youtube   Order Lisa's Books Lisa has published 5 books: Running Hot, Running to Extremes, Relentless, What your oncologist isn't telling you and her latest "Thriving on the Edge"  Check them all out at  https://shop.lisatamati.com/collections/books   Perfect Amino Supplement by Dr David Minkoff Introducing PerfectAmino PerfectAmino is an amino acid supplement that is 99% utilized by the body to make protein. PerfectAmino is 3-6x the protein of other sources with almost no calories. 100% vegan and non-GMO. The coated PerfectAmino tablets are a slightly different shape and have a natural, non-GMO, certified organic vegan coating on them so they will glide down your throat easily. Fully absorbed within 20-30 minutes! No other form of protein comes close to PerfectAminos Listen to the episode with Dr Minkoff here:    Use code "tamati" at checkout to get a 10% discount on any of their devices.   Red Light Therapy: Lisa is a huge fan of Red Light Therapy and runs a Hyperbaric and Red Light Therapy clinic. If you are wanting to get the best products try Flexbeam: A wearable Red Light Device https://recharge.health/product/flexbeam-aff/?ref=A9svb6YLz79r38   Or Try Vielights' advanced Photobiomodulation Devices Vielight brain photobiomodulation devices combine electrical engineering and neuroscience. To find out more about photobiomodulation, current studies underway and already completed and for the devices mentioned in this video go to www.vielight.com and use code “tamati” to get 10% off     Enjoyed This Podcast? If you did, subscribe and share it with your friends! If you enjoyed tuning in, then leave us a review and share this with your family and friends. Have any questions? You can contact my team through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts.  To pushing the limits, Lisa and team

Biohacking Beauty
Dr. Greg Kelly: Neurohacker: Revolutionary science to repair your DNA, maximize your performance, and perfect your skin

Biohacking Beauty

Play Episode Listen Later Apr 17, 2024 67:09


Did you know that it is believed that we were not evolutionarily programmed to age? That our bodies were made to reproduce and then essentially be depleted of the nutrients needed to stay youthful and feeling our best? Neurohacker is working to help bring new science to daily supplements, providing us with options to stimulate those depleted nutrients and molecules to decrease the speed of aging. In this episode of the Biohacking Beauty podcast, Amitay, CEO of Young Goose, sits down with Dr. Greg Kelly to discuss Neurohackers new NAD boosting stack, and how the powerhouse molecule of NAD fuels our cells, safeguards our DNA, and is synonymous with aging. Listen in and we examine the nuances of NAD's role in energy production and DNA repair, revealing the intricate network of metabolites and precursors that keep our bodies' engines running. Learn strategies for personal health and daily rituals that can enhance NAD levels and your overall well-being.What we discuss: (01:27) The Neurohacker Collective and the new NAD boosting stack to enhance your performance(06:45) How NAD impacts your DNA and senescent cells in your skin affect your entire body.(9:03) A brief history of molecules, NAD in the 90s to its use and new science now(12:36) NAD, a network of molecules that neurohackers are working to support to halt aging effects(16:29) NAD levels and ATP production as we age (18:33) Why stress leaves a scar, and how CD38, ATP and NAD all play a role in your appearance(20:51) Evolutionary theories about aging and why we can't out-eat the nutrients we need to feel our best(26:51) How the body responds to stressors, similarly to plant's responding to the environment(30:03) How cells choose multiple ways to do a job, and how we can support them(37:09) Magnesium and ATP, how they impact your cellular function(40:24) Aquaman magnesium and resveratrol, what they do for your cells(45:56) Intensity and time, and their impact on the performance curve(53:02) NAD and its impact on metabolic health(59:03) The optimal times to take NAD to maximize results (01:03:42) What to eat to support your NAD production To learn more about Young Goose:Use code PODCAST10 to get 10% off your first purchase, and if you're a returning customer use the code PODCAST5 to get 5% off at https://www.younggoose.com/Instagram: @young_goose_skincareTo learn more about Dr. Greg Kelly:Shop the Neurohacker Collective: https://neurohacker.com/shop/qualia-nadInstagram: https://www.instagram.com/neurohacker/Gregory Kelly is Director of Product Development at Neurohacker Collective, naturopathic physician (N.D.), and author of the book Shape Shift. He was the editor of the journal Alternative Medicine Review and has been an instructor at the University of Bridgeport in the College of Naturopathic Medicine, where he taught classes in Advanced Clinical Nutrition, Counseling Skills, and Doctor-Patient Relationships. Dr. Kelly has published hundreds of articles on natural medicine and nutrition, contributed three chapters to the Textbook of Natural Medicine, and has more than 30 journal articles indexed on Pubmed. His areas of expertise include nootropics, anti-aging and regenerative medicine, weight management, sleep and the chronobiology of performance and health.Resources:Spermidine research:

The Synthesis of Wellness
110. Intracellular NAD+ Testing, My Self-Experimentation, And Optimizing NAD+ Synthesis (Supporting The Salvage Pathway, Inhibiting CD38 Enzyme, & More)

The Synthesis of Wellness

Play Episode Listen Later Mar 29, 2024 23:14


In this episode, we delve into intracellular NAD+ testing and explore self-experimentation aimed at optimizing NAD+ synthesis. From supporting the salvage pathway, de novo synthesis, and the Preiss-Handler pathway to inhibiting the CD38 enzyme, we will uncover some key nutrients and precursors that will enhance NAD+ stores and production. Topics: 1. Importance of NAD+ - Cellular processes involving NAD+ - NAD+ as a coenzyme for numerous enzymes - Focus on energy metabolism 2. Energy Metabolism and NAD+ - Glycolysis and NAD+ - Krebs cycle and NAD+ - Electron transport chain and ATP production 3. Disruption of NAD+ to NADH Ratio - Inhibition of electron transport chain - Role of reactive oxygen species (ROS) 4. Strategies to Restore NAD+ Levels - De novo synthesis pathway of NAD+ - Preiss-Handler Pathway - Salvage pathway - Supporting pathways with supplements - CD38 Enzyme inhibition: how and why? 5. Personal Experimentation and Results Sharing - Self-experimentation to optimize intracellular NAD+ - Reporting results of experimentation Thank you to our episode sponsor: ⁠Dr. Morse's Daily Detox Kit⁠ Thanks for tuning in! Get Chloe's Book Today! "⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠" If you liked this episode, please leave a rating and review or share it to your stories over on Instagram. If you tag @synthesisofwellness, Chloe would love to personally thank you for listening! Follow Chloe on Instagram ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠@synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Follow Chloe on TikTok @chloe_c_porter Visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠synthesisofwellness.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to purchase products, subscribe to our mailing list, and more! Or visit ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠linktr.ee/synthesisofwellness⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to see all of Chloe's links, schedule a BioPhotonic Scanner consult with Chloe, or support the show! Thanks again for tuning in! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

Pushing The Limits
Understanding The NAD Story - Why NMN Is Not The Whole Story With Lisa Tamati

Pushing The Limits

Play Episode Listen Later Mar 28, 2024 33:34


This week on "Pushing the limits" we delve deep into the world of cellular health, focusing on NAD (Nicotinamide Adenine Dinucleotide) – the vital molecule that powers every cell in your body. Discover the intricacies of the NAD salvage pathway, the critical role of CD38 in NAD metabolism and how it impacts aging and cellular function. We'll explore groundbreaking research on NAMPT and NNMT enzymes and unveil the top supplements that support NAD levels for enhanced vitality and longevity. Whether you're a health enthusiast, a biohacker or someone looking to turn back the clock on cellular aging, this video is your ultimate guide to understanding and optimizing your body's NAD levels.  Key Topics Covered:  The importance of NAD in cellular health and aging.  An overview of the NAD salvage pathway.  The impact of CD38 on NAD depletion and how to counteract its effects.  In-depth analysis of NAMPT and NNMT enzymes in NAD synthesis.  Evidence-based supplements that boost NAD levels and support cellular rejuvenation.  Featured Supplements:  Nicotinamide Mononucleotide (NMN) Nicotinamide Riboside (NR) EGCG  Quercetin  Ergothioneine PQQ  TMG R-Alpha Lipoic Acid    Personalised Health Optimisation Consulting with Lisa Tamati Lisa offers solution focused coaching sessions to help you find the right answers to your challenges. Topics Lisa can help with:  Lisa is a Genetics Practitioner, Health Optimisation Coach, High Performance and Mindset Coach. She is a qualified Ph360 Epigenetics coach and a clinician with The DNA Company and has done years of research into brain rehabilitation, neurodegenerative diseases and biohacking. She has extensive knowledge on such therapies as hyperbaric oxygen,  intravenous vitamin C, sports performance, functional genomics, Thyroid, Hormones, Cancer and much more. She can assist with all functional medicine testing. Testing Options Comprehensive Thyroid testing DUTCH Hormone testing Adrenal Testing Organic Acid Testing Microbiome Testing Cell Blueprint Testing Epigenetics Testing DNA testing Basic Blood Test analysis Heavy Metals  Nutristat Omega 3 to 6 status and more  Lisa and her functional medicine colleagues in the practice can help you navigate the confusing world of health and medicine . She can also advise on the latest research and where to get help if mainstream medicine hasn't got the answers you are searching for whatever the  challenge you are facing from cancer to gut issues, from depression and anxiety, weight loss issues, from head injuries to burn out to hormone optimisation to the latest in longevity science. Book your consultation with Lisa    Join our Patron program and support the show Pushing the Limits' has been free to air for over 8 years. Providing leading edge information to anyone who needs it. But we need help on our mission.  Please join our patron community and get exclusive member benefits (more to roll out later this year) and support this educational platform for the price of a coffee or two You can join by going to  Lisa's Patron Community Or if you just want to support Lisa with a "coffee" go to  https://www.buymeacoffee.com/LisaT to donate $3   Lisa's Anti-Aging and Longevity Supplements  Lisa has spent years curating a very specialized range of exclusive longevity, health optimizing supplements from leading scientists, researchers and companies all around the world.  This is an unprecedented collection. The stuff Lisa wanted for her family but couldn't get in NZ that's what it's in her range. Lisa is constantly researching and interviewing the top scientists and researchers in the world to get you the best cutting edge supplements to optimize your life.   Subscribe to our popular Youtube channel  with over 600 videos, millions of views, a number of full length documentaries, and much more. You don't want to miss out on all the great content on our Lisa's youtube channel. Youtube   Order Lisa's Books Lisa has published 5 books: Running Hot, Running to Extremes, Relentless, What your oncologist isn't telling you and her latest "Thriving on the Edge"  Check them all out at  https://shop.lisatamati.com/collections/books   Perfect Amino Supplement by Dr David Minkoff Introducing PerfectAmino PerfectAmino is an amino acid supplement that is 99% utilized by the body to make protein. PerfectAmino is 3-6x the protein of other sources with almost no calories. 100% vegan and non-GMO. The coated PerfectAmino tablets are a slightly different shape and have a natural, non-GMO, certified organic vegan coating on them so they will glide down your throat easily. Fully absorbed within 20-30 minutes! No other form of protein comes close to PerfectAminos Listen to the episode with Dr Minkoff here:    Use code "tamati" at checkout to get a 10% discount on any of their devices.   Red Light Therapy: Lisa is a huge fan of Red Light Therapy and runs a Hyperbaric and Red Light Therapy clinic. If you are wanting to get the best products try Flexbeam: A wearable Red Light Device https://recharge.health/product/flexbeam-aff/?ref=A9svb6YLz79r38   Or Try Vielights' advanced Photobiomodulation Devices Vielight brain photobiomodulation devices combine electrical engineering and neuroscience. To find out more about photobiomodulation, current studies underway and already completed and for the devices mentioned in this video go to www.vielight.com and use code “tamati” to get 10% off     Enjoyed This Podcast? If you did, subscribe and share it with your friends! If you enjoyed tuning in, then leave us a review and share this with your family and friends. Have any questions? You can contact my team through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts.  To pushing the limits, Lisa and team

ASCO Daily News
Innovations in CAR T-Cell Therapy for Multiple Myeloma

ASCO Daily News

Play Episode Listen Later Mar 7, 2024 20:55


Drs. John Sweetenham and Shaji Kumar discuss the emergence of CAR T-cell therapy for multiple myeloma, its benefits and challenges for patients, and its potential role earlier in the treatment of disease. TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham from the UT Southwestern Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News Podcast.  Multiple myeloma is the second most common hematologic malignancy, and the American Cancer Society estimates that there will be more than 35,000 new cases of the disease diagnosed in the United States this year. The emergence of several novel therapies over the last decade has transformed the therapeutic landscape for multiple myeloma, and chimeric antigen receptor – or CAR T-cell therapy – is one of the newest treatments for this disease, which has created a great deal of buzz.  Dr. Shaji Kumar is an internationally renowned investigator of novel therapeutics and next-generation treatment options for patients with multiple myeloma, and I'm delighted to welcome him to the podcast today to discuss innovations in CAR T-cell therapy in this space. Dr. Kumar is a professor of medicine and chair of the Myeloma Group, as well as chair of research in the Division of Hematology at the Mayo Clinic in Rochester, Minnesota. He is also the editor-in-chief of The Hematologist.  You'll find our full disclosures available in the transcript of this episode, and disclosures of all guests on the podcast are available at asco.org/DNpod.  Shaji, it's great to have you on the podcast today. Dr. Shaji Kumar: Thanks, John. Dr. John Sweetenham: Shaji, to begin with, maybe we could ask you for an overview of where CAR T-cell therapy sits in multiple myeloma right now. We know that CAR T-cell therapy has improved the survival for some patients with myeloma in recent years. But of course, relapse still remains a problem. Can you tell us a little about the therapies that are currently approved for multiple myeloma in the CAR T-cell space, and what are the potential benefits and challenges of these products? Dr. Shaji Kumar: Absolutely. It has been a revolution, I think, in terms of therapies for multiple myeloma during the past decade. We have seen so many new treatments approved for myeloma, and consequently, the survival of patients with myeloma has significantly improved. Two decades ago, we used to tell patients a median survival of 3 years, and today we tell patients a median survival of 8 to 10 years, a number that is continuing to go up. And it is all because of the new treatments that have become available for patients, especially over the past decade, and CAR T-cell therapy has been a game changer.   Now, the main treatments that we were relying on for the past 2 decades have been the immunomodulatory drugs, the proteasome inhibitors, and more recently, the anti-CD38 monoclonal antibodies. Unfortunately, what we see in the clinic is that patients go through these therapies and various combinations of these agents, and often over the 6 to 10 years after the diagnosis, they often become refractory to these drugs. And then we are left with very few choices, if any, for controlling the disease. And that's where the CAR T cells have really made an impact.  Over the past several years, clinical trials have shown that CAR T-cell therapy is highly effective. In fact, when we look at the initial trials that have been done in this space, the majority of these CAR T cells have been targeted towards what we call BCMA, or a B-cell maturation antigen that is present on both normal and abnormal plasma cells. Now, the concept of CAR T cells has been around for a while, and we have already seen success in other hematological malignancies, but it has been a little late compared to the other diseases in terms of its arrival in the myeloma field. But over the past few years, we have seen some dramatic progress. We currently have two different CAR T cells that are approved and available in the clinic. We have idecabtagene vicleucel (ide-cel) and also ciltacabtagene which is also called cilta-cel. Both of these CAR T cells are targeted towards BCMA.   In the early trials conducted with both of these CAR T cells, we've seen patients who have become refractory to all the available therapies, and now upwards of 90% of these patients are responding to these CAR T cells. We are now seeing responses that we had typically not seen previously in any of the other therapies – not only the high response rates but also the depth of response. What we are seeing is a significant number of these patients – nearly half – of these patients can actually be minimal residual disease (MRD)-negative in the bone marrow after the CAR T-cell therapy. And this is clearly unprecedented in this myeloma space. Now, the approval for both these CAR T cells has been based on the experience in patients who have become refractory to the currently available therapies. And the ‘line in the sand' that the FDA has drawn for approval for these drugs has been at least 4 prior therapies. In those patients, when you look at the studies that have been done both for the ide-cel and the cilta-cel, it clearly demonstrates the advantages. And we can look at the data that's available in 3 groups. So we have the single-arm studies, the early phase I and phase 2 trials that have been done with both these CAR T cells. For ide-cel, we have the KarMMa trial, and for the cilta-cel, we have the CARTITUDE trials. In the initial studies, as I previously mentioned, we are seeing responses upwards of 90%, and we are seeing disease control that is lasting at least a year or more with these CAR T cells.   Now, of course, the question is, we do need randomized phase 3 trials to demonstrate that this is indeed true. Even before the phase 3 trials came along, there have been multiple case-control studies that have been done where the outcomes of patients getting these CAR T cells were compared to real-world controls or cohorts of patients who did not get these therapies. And these studies demonstrated that the outcomes of patients getting CAR T cells were significantly better than what has been shown in the real-world controlled population. And then finally, we have, of course, the phase 3 trials that have read out in patients with relapsed myeloma, in fact, in a group of patients in an earlier stage of the disease than who were studied in those single-arm studies. Now, based on the results from the single-arm studies, we got the approval from the FDA for the use of CAR T cells in this late stage of the disease. And with the phase 3 trials that have read out, both the KarMMa-3 trial and the CARTITUDE-4 trial again clearly demonstrate that these CAR T cells are much more effective than what we would have seen with the conventional therapies if those patients were assigned to those treatments. Now, clearly, it's not only a question of efficacy. We also know that they do come with some toxicities, and we have a good sense of the toxicities from those initial phase I and phase 2 trials. Now, as we have seen with the other diseases, the 2 major categories of toxicities that we see are the cytokine release syndrome and the neurological toxicity associated with CAR T-cell therapy.  In terms of the clinical features and the presentations, they are not different than what we have seen with the CAR T cells used in other hematological malignancies, but we do see different frequencies of these in the myeloma patient population. The cytokine release syndrome is something that is seen in a majority of the patients, at least in the lower grades. And over the time since we have been using CAR T-cell therapy, I think we have all become a lot more familiar with the management of the cytokine release syndrome, and we have very effective therapies to manage, and to some extent, maybe even prevent the onset of the cytokine release syndrome in patients undergoing CAR T-cell therapy.  The neurological toxicity is another toxicity that is unique to these immunological therapies, known as the ICANS, or the immune cell effector-associated neurological syndromes. And these, again, thankfully, are much less frequent than what we see with the cytokine release syndrome. But even with the ICANS and other neurological toxicities associated with CAR T-cell therapy, we have a better understanding of the biology behind it, and we also have better modalities to monitor the patients for these toxicities and intervene in an appropriate and timely manner to take care of them.  In addition to the ICANS and the cytokine release syndrome, we certainly do see other toxicities as well. We do see hematological toxicities, which are common for many of the treatments we use for hematological malignancies. Thankfully, these other toxicities can be easily managed. They often reverse themselves over time and haven't really posed any major hurdles in terms of the utilization of these modalities of therapy for patients with myeloma. Dr. John Sweetenham: Okay, that's great. Thank you very much, Shaji. I'll return to some of the potential late effects of CAR T-cell therapy in a moment. But before we get to that, as you know, in other hematologic malignancies, there has been a trend in recent years to moving CAR T-cell therapy further up the therapeutic algorithm, as it were. So there is consideration being given to using this as a first-line or second-line therapy. Do you think there is a potential role for CAR T cell earlier in the treatment of multiple myeloma? For example, could you see a time when it may be used as second-line treatment for this disease? Dr. Shaji Kumar: Absolutely. I think that's a very good point. And I think, just as with other cancers and as with myeloma, too, with many of the therapies we use for myeloma in the newly diagnosed setting or the time of first relapse, were all initially tested in these later relapses. We are following the same script even for the CAR T cells. In fact, the 2 phase 3 trials, the KarMMa-3 trial and the CARTITUDE-4 trial, enrolled patients in the earlier lines of therapy, either 1 prior line or 2 prior lines for these trials. And what we have seen with both phase 3 trials is that the outcomes, both the progression-free survival outcomes and the response rates, are significantly better compared to the standard-of-care therapies that these patients would have otherwise received.  Now, what is unclear at this point is, does every patient at the time of the first relapse need a CAR T-cell therapy, or can we be more selective in terms of deciding which particular subgroup of patients can benefit more from this CAR T-cell therapy in different lines or different relapses? The bottom line is, I think the data that we have right now clearly points towards the utility of CAR T-cell therapy at earlier lines of treatment. The question now is, which patients do we need to do at which stage? In fact, when you look at the newly diagnosed setting, there are ongoing clinical trials that are looking at replacing autologous stem cell transplant with CAR T-cell therapy. Those phase 3 trials are currently enrolling where patients are being randomized to either the autologous stem cell transplant, which is considered a standard of care for eligible patients, or giving them a CAR T-cell therapy. Similarly, even in transplant-ineligible patients, trials are exploring the possibility of using CAR T-cell therapy instead of giving patients a prolonged course of maintenance and consolidation.  One of the beauties with the CAR T-cell therapy right now is that it's a one-time treatment. You get the treatment and you do not get any additional therapies after that. It's a protocol that is being debated – whether we will need maintenance therapies after CAR T-cell therapy, but I think that is something that will have to be explored in the context of clinical trials. But certainly, I think over the next 5 years, we will see the CAR T-cell therapy moving to earlier and earlier lines of therapy. My guess is in 5 years, there will be a subset of patients where we would offer them CAR T-cell as part of the first-line therapy, some others, maybe based on disease and patient characteristics, we might use it at the time of first or second relapse.   Dr. John Sweetenham: Great, thank you. Just to return to toxicities and some of the potential late effects. As you know, last November, the FDA launched an investigation to determine whether CAR T-cell therapy can, in rare cases, cause secondary cancers. You may remember that this was in response to reports of T-cell malignancies in patients who had received various types of CAR T-cell immunotherapies. The FDA determined that the risk of T-cell malignancies is applicable to all of the currently approved BCMA-directed and CD19-directed genetically modified autologous CAR T-cell immunotherapies. Could you care to comment on this whether you have seen any evidence of this in your own work, and whether the events and the FDA investigation have impacted your clinical research or your clinical practice in any way in terms of patient monitoring or maybe in terms of trial approval? Dr. Shaji Kumar: This has been an important observation. As with all new therapies, whenever the question of long-term toxicities is brought up, especially second malignancies, it is something that needs to be looked into very carefully, and I think the FDA is doing exactly that. There have been reports of second cancers, particularly T-cell cancers. In fact, there were some statements that came out recently from the FDA where they commented on the fact that they had seen 22 cases of T-cell cancers by the end of 2023. And, in fact, in 3 of those cases where genetic sequencing was performed, they did notice that the genetic material or the chimeric antigen receptor was inserted into these cancer cells as part of the process. So I think there is a lot more work that needs to be done in terms of understanding the mechanism and probably also understanding how prevalent these instances are.  But I think, based on what we know as of now, these cases form a very tiny fraction of the total number of CAR T-cell therapies that have been used in patients with lymphoma and myeloma. In our own day-to-day practice, this has not really affected how we view this therapy. It clearly has made a significant impact for patients with no other treatment options. So in our daily practice, we continue to use CAR T-cell therapy as we have done before these reports came out. But we do inform patients about the risk and what we know about the risk of these T-cell malignancies.   In addition to T-cell malignancies, there have also been reports of myelodysplastic syndromes in patients undergoing CAR T-cell therapy. Again, it is important to remember that, at least in the myeloma setting, many of these patients have had multiple lines of therapy, often with drugs that can cause second malignancies, particularly myelodysplastic syndrome. So I think a lot more work needs to be done in terms of understanding what is the direct impact of CAR T-cell therapy versus what was lurking underneath because of the treatments that these patients had previously received. So I think it is important for us to continue to be very diligent, as with any new therapies that we introduce for the treatment of our patients. But at the same time, understand that, in the context of the benefits that these therapies bring to our patients, especially when they have no other treatment options.  Dr. John Sweetenham: Absolutely. So, at least for now, and probably in the longer term, the benefits of the therapy certainly appear to outweigh the risks, although it is important not to underestimate or minimize those risks.   I wanted to change direction a little bit and talk a little bit in the final question about care disparities and CAR T cell. Of course, CAR T-cell therapy is typically offered at large cancer centers and is very expensive. This means that there are issues of access to treatment. In addition, the literature shows us that non-Hispanic Black individuals are twice as likely to develop multiple myeloma compared to their White counterparts. Furthermore, at least right now, Black patients are less likely to receive these novel CAR T-cell therapies and continue to be underrepresented in clinical trials. So, this is a big, complex question, but can you talk a little bit about how outcomes differ between racial and ethnic groups who actually receive CAR T-cell therapy for multiple myeloma? And could you address what you think are the most appropriate strategies for minimizing the disparities in access? Dr. Shaji Kumar: That's a very, very important question, particularly in the context of multiple myeloma, where African American individuals are at a higher risk of getting plasma cell malignancies. I think we need to think about this in the context of what we know about disparities even before the CAR T cell came along. There has been a good amount of literature that has looked at the outcomes based on the types of therapies that could be impacted by this. There have been studies that have looked at cooperative group trials, which often have a good representation of minorities and have shown that if patients have equal access to advanced therapies that we have, their outcomes are comparable or sometimes even better for African American patients compared to Caucasian patients. So I think it's very important that the treatment strategies that we develop are equally accessible to everyone.  In terms of CAR T-cell therapy or immunotherapies, I don't think we have any concrete evidence to suggest that there is any difference in outcomes. And I think it's reasonable to assume that if patients are exposed to similar therapies, they will have similar outcomes, even in the context of immunotherapies. But at the same time, I think we must continue to study this diligently, and the only way to do that is to ensure that clinical trials include patients reflective of society in general. This will allow us to understand if any differences exist. In addition, I think there is a serious risk that with these expensive therapies, this gap can only widen. And I think that is one reason that we must be proactive, particularly with therapies like CAR T-cell therapy, which not only are expensive but also require quite a bit of logistical support for patients to go to larger centers to get these therapies, stay around these larger centers for upwards of a couple of months, which means they are living outside of their usual societal structure, and ensure there is access to the resources that are needed to enable them to do that. So I think there is a lot that is still unknown, but I think we really need to be proactive in ensuring equal access to these therapies. Dr. John Sweetenham: Yes. Thanks for a very thoughtful response to that question, also for the work that you are obviously doing to help address this extremely important issue.  I'd like to thank you for sharing your insights with us today and for the extraordinary work that you're doing and your team are doing to advance care for patients with multiple myeloma. Dr. Shaji Kumar: Thank you, John. Dr. John Sweetenham: And thank you also to our listeners for joining us today. If you value the insights you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.  Disclaimer:  The purpose of this podcast is to educate and inform. It is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. The guests on this podcast express their own opinions, experience, and conclusions. Guest statements do not necessarily reflect the opinions of ASCO. Mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Find out more about today's guest:    Dr. Shaji Kumar @myelomaMD   Follow ASCO on social media:       @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn       Disclosures:      Dr. John Sweetenham:   Consulting or Advisory Role: EMA Wellness     Dr. Shaji Kumar: Consulting or Advisory Role: Takeda, Janssen Oncology, Genentech/Roche, Abbvie, Bristol-Myers Squibb/Celgene, Pfizer, Regeneron, Sanofi, K36 Research Funding (Inst.): Takeda, Abbvie, Novartis, Sanofi, Janssen Oncology, MedImmune, Roche/Genentech, Carsgen Therapeutics Ltd., Allogene Therapeutics, GlaxoSmithKline, Regeneron, Bristol-Myers Squibb/Celgene Travel, Accommodations, Expenses: Abbvie, Pfizer

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast
Thomas G. Martin, III, MD - The A-Team Against Relapsed/Refractory Myeloma: Community Strategies for Enhancing Outcomes With Potent CD38 Antibody Platforms

PeerView Clinical Pharmacology CME/CNE/CPE Audio Podcast

Play Episode Listen Later Dec 12, 2023 62:15


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/IPCE information, and to apply for credit, please visit us at PeerView.com/NRA865. CME/MOC/NCPD/IPCE credit will be available until November 29, 2024.The A-Team Against Relapsed/Refractory Myeloma: Community Strategies for Enhancing Outcomes With Potent CD38 Antibody Platforms In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sanofi.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerThomas G. Martin, III, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for GlaxoSmithKline and Pfizer.Grant/Research Support from Bristol Myers Squibb; Janssen Pharmaceuticals, Inc.; and Sanofi.Faculty/PlannerBeth Faiman, PhD, MSN, APN-BC, AOCN, BMTCN, FAAN, FAPO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for GlaxoSmithKline; Janssen Pharmaceuticals, Inc.; Karyopharm Therapeutics; Pfizer; and Sanofi.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast
Thomas G. Martin, III, MD - The A-Team Against Relapsed/Refractory Myeloma: Community Strategies for Enhancing Outcomes With Potent CD38 Antibody Platforms

PeerView Oncology & Hematology CME/CNE/CPE Video Podcast

Play Episode Listen Later Dec 12, 2023 61:55


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/IPCE information, and to apply for credit, please visit us at PeerView.com/NRA865. CME/MOC/NCPD/IPCE credit will be available until November 29, 2024.The A-Team Against Relapsed/Refractory Myeloma: Community Strategies for Enhancing Outcomes With Potent CD38 Antibody Platforms In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sanofi.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerThomas G. Martin, III, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for GlaxoSmithKline and Pfizer.Grant/Research Support from Bristol Myers Squibb; Janssen Pharmaceuticals, Inc.; and Sanofi.Faculty/PlannerBeth Faiman, PhD, MSN, APN-BC, AOCN, BMTCN, FAAN, FAPO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for GlaxoSmithKline; Janssen Pharmaceuticals, Inc.; Karyopharm Therapeutics; Pfizer; and Sanofi.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

PeerView Internal Medicine CME/CNE/CPE Video Podcast
Thomas G. Martin, III, MD - The A-Team Against Relapsed/Refractory Myeloma: Community Strategies for Enhancing Outcomes With Potent CD38 Antibody Platforms

PeerView Internal Medicine CME/CNE/CPE Video Podcast

Play Episode Listen Later Dec 12, 2023 61:55


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/IPCE information, and to apply for credit, please visit us at PeerView.com/NRA865. CME/MOC/NCPD/IPCE credit will be available until November 29, 2024.The A-Team Against Relapsed/Refractory Myeloma: Community Strategies for Enhancing Outcomes With Potent CD38 Antibody Platforms In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sanofi.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerThomas G. Martin, III, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for GlaxoSmithKline and Pfizer.Grant/Research Support from Bristol Myers Squibb; Janssen Pharmaceuticals, Inc.; and Sanofi.Faculty/PlannerBeth Faiman, PhD, MSN, APN-BC, AOCN, BMTCN, FAAN, FAPO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for GlaxoSmithKline; Janssen Pharmaceuticals, Inc.; Karyopharm Therapeutics; Pfizer; and Sanofi.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

PeerView Internal Medicine CME/CNE/CPE Audio Podcast
Thomas G. Martin, III, MD - The A-Team Against Relapsed/Refractory Myeloma: Community Strategies for Enhancing Outcomes With Potent CD38 Antibody Platforms

PeerView Internal Medicine CME/CNE/CPE Audio Podcast

Play Episode Listen Later Dec 12, 2023 62:15


This content has been developed for healthcare professionals only. Patients who seek health information should consult with their physician or relevant patient advocacy groups.For the full presentation, downloadable Practice Aids, slides, and complete CME/MOC/NCPD/IPCE information, and to apply for credit, please visit us at PeerView.com/NRA865. CME/MOC/NCPD/IPCE credit will be available until November 29, 2024.The A-Team Against Relapsed/Refractory Myeloma: Community Strategies for Enhancing Outcomes With Potent CD38 Antibody Platforms In support of improving patient care, this activity has been planned and implemented by PVI, PeerView Institute for Medical Education, and HealthTree Foundation for Multiple Myeloma. PVI, PeerView Institute for Medical Education, is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.SupportThis activity is supported by an educational grant from Sanofi.Disclosure PolicyAll relevant conflicts of interest have been mitigated prior to the commencement of the activity.Faculty/Planner DisclosuresChair/PlannerThomas G. Martin, III, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for GlaxoSmithKline and Pfizer.Grant/Research Support from Bristol Myers Squibb; Janssen Pharmaceuticals, Inc.; and Sanofi.Faculty/PlannerBeth Faiman, PhD, MSN, APN-BC, AOCN, BMTCN, FAAN, FAPO, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for GlaxoSmithKline; Janssen Pharmaceuticals, Inc.; Karyopharm Therapeutics; Pfizer; and Sanofi.Planning Committee and Reviewer DisclosuresPlanners, independent reviewers, and staff of PVI, PeerView Institute for Medical Education, do not have any relevant financial relationships related to this CE activity unless listed below.

Research To Practice | Oncology Videos
Multiple Myeloma | What Clinicians Want to Know About Anti-CD38 Antibodies in the Management of Multiple Myeloma

Research To Practice | Oncology Videos

Play Episode Listen Later Oct 9, 2023 47:16


Featuring an interview with Prof Philippe Moreau, including the following topics: Perspectives on efficacy outcomes with and toxicity profiles of daratumumab and isatuximab (0:00) Selection of an anti-CD38 antibody for initial treatment of multiple myeloma (MM) (7:28) Approach to maintenance therapy for transplant-eligible patients with MM (15:47) Management of MM in older patients; treatment approaches for t(11;14) MM (22:47) Management of relapsed/refractory MM (29:49) Management of anti-CD38 antibody-associated side effects (35:45) Other relevant clinical scenarios in MM — Plasma cell leukemia, smoldering myeloma (41:19) Perspectives on the future landscape of up-front treatment for MM (45:02) CME information and select publications

Research To Practice | Oncology Videos
Multiple Myeloma | What Clinicians Want to Know About Anti-CD38 Antibodies in the Management of Multiple Myeloma (Companion Faculty Lecture)

Research To Practice | Oncology Videos

Play Episode Listen Later Oct 9, 2023 28:48


Featuring a slide presentation and related discussion from Dr Philippe Moreau, including the following topics: General overview of anti-CD38 antibodies in therapy for multiple myeloma (MM) (0:00) Anti-CD38 antibodies as part of first-line therapy for transplant-ineligible patients with MM (2:35) Quadruplet versus triplet induction regimens with anti-CD38 antibodies for newly diagnosed, transplant-eligible patients with MM (7:44) Clinical trial data with anti-CD38 antibodies for patients with MM at first relapse (13:02) Treatment options for patients with MM at second relapse and beyond (18:09) Subcutaneous formulations of daratumumab and isatuximab; CD38 as a target for other therapeutic strategies (21:00) CME information and select publications

Hematologic Oncology Update
What Clinicians Want to Know About Anti-CD38 Antibodies in the Management of Multiple Myeloma

Hematologic Oncology Update

Play Episode Listen Later Oct 9, 2023 47:30


Prof Philippe Moreau from the University Hospital of Nantes in France discusses anti-CD38 antibody-based treatment approaches for newly diagnosed and relapsed/refractory multiple myeloma, moderated by Dr Neil Love.

Oncology Today with Dr Neil Love
What Clinicians Want to Know About Anti-CD38 Antibodies in the Management of Multiple Myeloma

Oncology Today with Dr Neil Love

Play Episode Listen Later Oct 6, 2023 47:30


Professor Philippe Moreau from the University Hospital of Nantes in France discusses anti-CD38 antibody-based treatment approaches for newly diagnosed and relapsed/refractory multiple myeloma moderated by Dr Neil Love. Produced by Research To Practice. CME information and select publications here (https://www.researchtopractice.com/MonoclonalAntibodiesMM23)

The Synthesis of Wellness
29. NAD+, Its Use in Energy Metabolism, Factors That Deplete NAD+ (Including Aging), 6 Strategies to Increase NAD+ Levels, & Thoughts on Using NAD+ Therapies for Mold Illness

The Synthesis of Wellness

Play Episode Listen Later Aug 16, 2023 40:07


In today's episode, we are diving into NAD+ and exploring how it is a critical component for breaking down fuel, such as glucose, and ultimately converting that fuel to ATP. We will explore various factors that deplete NAD+ or decrease the NAD+/NADH ratio as well as 6 proven strategies to increase NAD+ within the body. Lastly, we wrap up the episode with a conversation pertaining to the use of NAD+ therapy for CIRS/Biotoxin illness, specifically Mold Illness. Thanks so much for tuning it! Topics: 1. Understanding NAD+ and Its Role - Definition of NAD+ and NADH - Explanation of coenzymes in chemical reactions - NAD+ and NADH as coenzymes for electron transfer - Role in glucose metabolism and energy production - Importance of NAD+ for various cellular functions 2. Glycolysis and NAD+ - Illustration of glucose metabolism and insulin release - Role of GLUT4 transporters in glucose entry into cells - Introduction to glycolysis and its steps - Role of NAD+ as a coenzyme in glycolysis - Generation of NADH during glycolysis 3. TCA (Krebs) Cycle and NAD+ - Transition of pyruvate to acetyl-coA - Overview of the krebs cycle and its steps - NAD+ as a coenzyme in the krebs cycle - Accumulation of NADH during the cycle 4. Electron Transport Chain and NADH - Movement of pyruvate into the mitochondria - Role of NADH as an electron donor in the electron transport chain (ETC) - ATP production through the ETC 5. Factors Disrupting NAD+ Balance - Impact of toxins and pesticides on the ETC - Role of drugs, like NSAIDs, in inhibiting the ETC - Generation of reactive oxygen species (ROS) - Role of ROS in mitochondrial damage and NAD+ depletion - Link between NAD+ decline and aging 6. Consequences of NAD+ Depletion - Effect of NAD+ reduction on metabolism - Connection between NAD+ and metabolic diseases - Therapeutic potential of NAD+ in age-related diseases 7. 6 Strategies for NAD+ Restoration - Which supplemental NAD+ precursors are more effective - Inhibition of the CD38 enzyme using dietary nutrients - NAD+ IVs and patches: cost and quality - Intermittent fasting - Exercise and NAD+ - Other less well-known lifestyle factors that have a big impact on NAD+ 8. NAD+ Therapies to Support Recovery from Mold Illness - Link between NAD+ depletion and mold illness - Thoughts on and logic behind the use of NAD+ therapies for CIRS recovery Thanks for tuning in! If you liked this episode, please leave a rating and review or share it to your stories over on Instagram. If you tag @synthesisofwellness, Chloe would love to personally thank you for listening! Follow Chloe on Instagram @synthesisofwellness Follow Chloe on TikTok @chloe_c_porter Visit ⁠synthesisofwellness.com⁠ to purchase products, subscribe to our mailing list, and more! Or visit ⁠linktr.ee/synthesisofwellness⁠ to see all of Chloe's links, schedule a BioPhotonic Scanner consult with Chloe, or support the show! Thanks again for tuning in! --- Support this podcast: https://podcasters.spotify.com/pod/show/chloe-porter6/support

Pharmacy Podcast Network
Aligning Treatment Goals and Value-Based Care in Newly Diagnosed Multiple Myeloma | i3Health

Pharmacy Podcast Network

Play Episode Listen Later May 17, 2023 15:44


i3Health has developed a dual part education activity for pharmacists on Multiple myeloma with special guest Joseph A. Kalis, PharmD, BCOP and Ambulatory Oncology Pharmacy Specialist.  Multiple myeloma is a clonal plasma cell malignancy characterized by several cytogenetic alterations. Treatment planning for individual patients is complicated by factors such as age, frailty, comorbidities, eligibility for autologous stem cell transplantation, and risk stratification.  Clinicians need to continually update their working knowledge of emerging data and consensus recommendations that can rationally inform clinical decision making. In Module 1 of this continuing pharmacy education (CPE)–approved activity, Joseph A. Kalis, PharmD, BCOP, Ambulatory Oncology Clinical Pharmacy Specialist at the University of Colorado Health, will explore evolving treatment paradigms in newly diagnosed multiple myeloma, including the efficacy and safety of anti-CD38 monoclonal antibodies and supportive care considerations for their use.

New Frontiers in Functional Medicine
SPONSORED | The Role of NAD+ in Aging, Chronic Disease, and Epigenetics with Dr. Nichola Conlon

New Frontiers in Functional Medicine

Play Episode Listen Later Apr 3, 2023 64:11


One fascinating and incredibly important molecule to pay attention to in the field of healthy longevity is nicotinamide adenine dinucleotide (NAD+). It's literally in every cell and contributes to over 300 different reactions in the body as a coenzyme substrate. Dr. Nichola Conlon, PhD, is an expert on NAD+ and launched Nuchido Laboratories to rigorously test and develop a NAD+ booster supplement packed with epinutrients. She joins me in this ridiculously interesting conversation where she explains role of NAD+ as a signaling molecule, its relationship with longevity proteins sirtuins, its impact on multiple hallmarks of aging, its relationship to the salvage pathway, NNMT and CD38. And that just touches the surface of all we discuss in today's talk! I'm thrilled to have her with me and hope you enjoy listening. ~DrKF