Podcasts about myeloid

Drs. Sanam Loghavi and Amer Zeidan delve into the history behind the recent classification split between the World Health Organization (WHO) and the International Consensus Classification (ICC) for myeloid and lymphoid malignancies, and how a few years of minor disagreement have culminated in a unified system. They explore the critical differences in how myeloid and lymphoid neoplasms are now categorized, what this alignment means for pathologists, oncologists, regulators, and patients, when the new classification will take effect, and how it is expected to influence research, diagnosis, and clinical care. Check out Chadi's website for all Healthcare Unfiltered episodes and other content. www.chadinabhan.com/ Watch all Healthcare Unfiltered episodes on YouTube. www.youtube.com/channel/UCjiJPTpIJdIiukcq0UaMFsA

Daniel Getts, the CEO and Founder of Myeloid Therapeutics is focused on the role of myeloid cells in the immune response to solid tumors. These cells are the first responders in the immune system and play a crucial role in bridging the innate and adaptive immune response. The Myeloid Therapeutics' mRNA technology activates myeloid cells in tumors, making the tumor microenvironment hot and attracting other immune cells to fight the cancer. Daniel explains, "The ability to harness our immune systems has revolutionized how we treat cancer. Unfortunately, we still have a long way to go, and if you think about some of the worst of the worst cancers, such as pancreatic cancer, liver cancer, and so on, immunotherapy has still not gotten us to a place where we can solve this. It's our mission at Myeloid Therapeutics to overcome these challenges. We've uncovered a lot of really interesting things about these cancers in the last 20 years, and we've been harnessing that knowledge."  "Myeloid cells are at the heart of the immune system. They're the first responders. So, if you have an infection or bump your knee, these cells are immediately called to the site to wall off and prevent any more damage. However, they also serve as the bridge to adaptive immunity, the T cells and the B cells, which are also important for integrating an immune response. In the context of COVID vaccines, we talk about antibodies and T cells, it's the myeloid cells that are essential. In the context of what we've been learning, immunotherapy, up until recently, had been very focused on T cells and how to short-circuit the whole system just by using or activating those cells to kill cancer. And what we're starting to learn is to harness the full capability of our own immune systems, you've got to go back to the start. You've got to harness the myeloid compartment so you can orchestrate all immune elements to kill cancer." #MyeloidTherapeutics #MyeloidCells #ImmuneSystem #SolidTumors #Cancer #ImmuneResponse #Oncology #TumorMicroenvironment myeloidtx.com Download the transcript here

Daniel Getts, the CEO and Founder of Myeloid Therapeutics, is focused on the role of myeloid cells in the immune response to solid tumors. These cells are the first responders in the immune system and play a crucial role in bridging the innate and adaptive immune response. The Myeloid Therapeutics' mRNA technology activates myeloid cells in tumors, making the tumor microenvironment hot and attracting other immune cells to fight the cancer. Daniel explains, "The ability to harness our immune systems has revolutionized how we treat cancer. Unfortunately, we still have a long way to go, and if you think about some of the worst of the worst cancers, such as pancreatic cancer, liver cancer, and so on, immunotherapy has still not gotten us to a place where we can solve this. It's our mission at Myeloid Therapeutics to overcome these challenges. We've uncovered a lot of really interesting things about these cancers in the last 20 years, and we've been harnessing that knowledge."  "Myeloid cells are at the heart of the immune system. They're the first responders. So, if you have an infection or bump your knee, these cells are immediately called to the site to wall off and prevent any more damage. However, they also serve as the bridge to adaptive immunity, the T cells and the B cells, which are also important for integrating an immune response. In the context of COVID vaccines, we talk about antibodies and T cells, it's the myeloid cells that are essential. In the context of what we've been learning, immunotherapy, up until recently, had been very focused on T cells and how to short-circuit the whole system just by using or activating those cells to kill cancer. And what we're starting to learn is to harness the full capability of our own immune systems, you've got to go back to the start. You've got to harness the myeloid compartment so you can orchestrate all immune elements to kill cancer." #MyeloidTherapeutics #MyeloidCells #ImmuneSystem #SolidTumors #Cancer #ImmuneResponse #Oncology #TumorMicroenvironment myeloidtx.com Listen to the podcast here

In today's episode, we'll discuss time-limited triplet therapy in relapsed or refractory CLL. Zanubrutinib, venetoclax and obinutuzumab induced deep remissions, and was well tolerated, even in very high-risk patients, and those with prior exposure to targeted therapies. After that: researchers chronicle the development of a patient-reported outcome measure for sclerosis associated with chronic GVHD—graft-versus-host disease. The new symptom scale—currently undergoing validation studies—may provide valuable information regarding severity, functional impact, and response to therapy. Finally, a study of changes in population dynamic rates that underlie inflammation-associated myeloid bias. The work demonstrates the use of mathematical models to deliver critical biological insights and uncover underlying mechanisms.Featured Articles:MRD-guided zanubrutinib, venetoclax, and obinutuzumab in relapsed CLL: primary end point analysis from the CLL2-BZAG trialDevelopment of the Lee Symptom Scale–Skin Sclerosis for chronic GVHD–associated sclerosisPopulation dynamics modeling reveals that myeloid bias involves both HSC differentiation and progenitor proliferation biases

In this episode, we delve into the key clinically relevant abstracts in leukemia and myeloid neoplasms with Dr. Jayastu Senapati from the MD Anderson Cancer Center. Here are the links to the abstracts we discussed: Older AML: Ven+HMA vs 7+3Abstract 450: https://ash.confex.com/ash/2024/webprogram/Paper210320.htmlAbstract 971: https://ash.confex.com/ash/2024/webprogram/Paper202801.htmlAbstract 969: https://ash.confex.com/ash/2024/webprogram/Paper199267.htmlVenetoclax resistance mechanismshttps://pubmed.ncbi.nlm.nih.gov/39478230/FLAG-GO vs FLAG-IDA https://ashpublications.org/blood/article/144/Supplement%201/1513/532742/Gemtuzumab-Ozogamicin-Added-to-Fludarabine CPX-351: Abstract 55: https://ash.confex.com/ash/2024/webprogram/Paper207094.htmlAbstract 60: https://ash.confex.com/ash/2024/webprogram/Paper200413.htmlMenin Inhibitors Abstract 211 https://ash.confex.com/ash/2024/webprogram/Paper194384.htmlAbstract 212 https://ash.confex.com/ash/2024/webprogram/Paper207106.htmlAbstract 213 https://ash.confex.com/ash/2024/webprogram/Paper194827.htmlAbstracts 214 https://ash.confex.com/ash/2024/webprogram/Paper198218.htmlAbstract 215 https://ash.confex.com/ash/2024/webprogram/Paper198218.htmlAbstract 216 https://ash.confex.com/ash/2024/webprogram/Paper204375.html FLT3 inhibitors Abstract 221: https://ash.confex.com/ash/2024/webprogram/Paper201595.html MDS Abstract 349: https://ash.confex.com/ash/2024/webprogram/Paper194510.html ATRA in MDS:  https://ash.confex.com/ash/2024/webprogram/Paper200433.html  

This week Jonathan is joined by Joshua Zeidner, Associate Professor of Medicine, University of North Carolina School of Medicine, USA. Together, they discuss findings from recent research and treatment options for acute myeloid leukaemia and myelodysplastic syndrome. Timestamps:     (00:00)- Introduction    (01:57)- Joshua's love for the New York Giants  (04:28)- Treatment outcomes in IDH1 and IDH2-mutated acute myeloid leukaemia (AML)  (08:05)- Safety and efficacy of new agents in AML  (17:00)- Treatments for patients with AML with a TP53 mutation  (22:02)- Reliance on transfusion in myelodysplastic syndrome (MDS)  (25:44)- The time from research lab to bedside in drugs to treat AML and MDS  (30:50)- Joshua's three wishes for healthcare   (35:13)- Outro   

When patients with recurrent high-grade glioblastoma were treated with autologous myeloid dendritic cells, they had clinical responses described as “encouraging” in a Phase I clinical trial reported at the ESMO Congress 2024. Cells harvested from each patient were injected directly into the resection cavity brain tissue lining after surgery. Patients also received intracranial injections of the checkpoint inhibitor combination: nivolumab + ipilimumab. At the conference, Oncology Times reporter Peter Goodwin caught up with lead author of the study, Bart Neyns, MD, PhD, Head of Medical Oncology at the Vrije Universiteit Brussel in the University Hospital Brussels Faculty of Medicine & Pharmacy in Belgium.

Ximena Jordan-Bruno, MD, University of Pennsylvania, Philadelphia, PA Recorded on June 4, 2024 Ximena Jordan-Bruno, MD Assistant Professor, Division of Hematology/Oncology University of Pennsylvania Philadelphia, PA Join us for this fascinating episode, where Dr. Ximena Jordan-Bruno from the University of Pennsylvania explores hereditary myeloid and hematologic disorders, covering their classifications, mutations, and related germline predisposition syndromes. Learn about key clinical features, diagnostic approaches, the role of genetic counseling, and future research directions. Tune in today for valuable updates to enhance your understanding and practice!

Dr. Kipp Weiskopf is a Valhalla Fellow at the Whitehead Institute. His research focuses on unlocking the therapeutic potential of macrophages for the benefit of cancer patients. He talks about the role of macrophages in the tumor environment and how targeting the CD47/SIRPα axis can induce phagocytosis of cancer cells. He also discusses starting spin-off companies to advance cancer therapies.

This podcast follows the case of a 58 year old man who presented to the haematology department at Flinders Medical Centre with intravascular coagulation and leukocytosis. He was diagnosed with acute myeloid leukaemia and treated on standard cytarabine and daunorubicin combination therapy. Nine days after initiation, the patient developed painless diplopia and ptosis, and the story is picked up with a referral to the neurology department. GuestsAssociate Professor Stephen Bacchi (Lyell McEwin Hospital; University of Adelaide)Dr James Triplett FRACP (Flinders Medical Centre, consultant neurologist) ProductionProduced by Stephen Bacchi and Mic Cavazzini. Music licenced from Epidemic Sound includes ‘Rockin' for Decades' by Blue Texas and ‘Brighton Breakdown' by BDBs. Image created and copyrighted by RACP. Editorial feedback kindly provided by RACP physicians Aidan Tan and Brandon Stretton.Please visit the Pomegranate Health web page for a transcript and supporting references. Login to MyCPD to record listening and reading as a prefilled learning activity.Key Reference and Learning Points (Spoiler Alert)********Painless progressive mononeuritis multiplex secondary to AML associated neuroleukemiosis [J Neuroimmunol. 2023]  (1) Chemotherapy can have neurological complications, including chemotherapy induced peripheral neuropathy (e.g., oxaliplatin).(2) A third (oculomotor) cranial nerve palsy has multiple possible causes, which can be divided into painful vs painless causes, and compressive (classically with pupillary involvement) vs non-compressive (can spare pupil, as with microvascular insult) causes.(3) Conduction block is shown by a significant reduction in compound muscle action potential, between proximal and distal stimulation, the criteria for which varies by nerve.(4) Ascertaining whether conduction block occurs at compressible vs non-compressible sites can be a useful distinguishing feature for the various possible causes e.g. including compression, demyelination, and ischaemia, and (5) Mononeuritis multiplex, while classically associated with a vasculitic neuropathy, has a number of causes, including leukaemia. This is the very rare condition known as neuroleukemiosis.

BUFFALO, NY- July 19, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on July 2, 2024, entitled, “DDX41 and its unique contribution to myeloid leukemogenesis.” In this new editorial, researcher Hirotaka Matsui from the National Cancer Center Hospital in Tokyo, Japan, and Kumamoto University discusses myeloid neoplasms. Until the early 2000s, myeloid neoplasms attributable to genetic backgrounds were considered exceedingly rare, with notable exceptions limited to those arising as components of systemic syndromes such as Fanconi anemia and Li-Fraumeni syndrome. Historically, no hematopoietic-specific tumor syndromes had been identified until 1999, when RUNX1 was implicated as the causative gene for familial platelet disorder with a predisposition to acute myeloid leukemia (AML). Subsequently, in 2004, CEBPA was recognized as another critical gene responsible for inherited AML. The subsequent advent and widespread application of comprehensive genetic analysis facilitated the identification of germline pathogenic variants in genes such as ANKRD26, ETV6, and GATA2 among patients with myeloid neoplasms that developed against a background of inherited thrombocytopenia or systemic disorders. It is now established that genetic predisposition is present in approximately 10% of myeloid neoplasms, underscoring the fact that myeloid neoplasms with a genetic background are by no means exceptional. “Among these, myeloid neoplasms caused by DDX41 variants are particularly noteworthy due to their distinct disease phenotype and pathogenesis [2].” DOI - https://doi.org/10.18632/oncotarget.28603 Correspondence to - Hirotaka Matsui - hmatsui@ncc.go.jp Video short - https://www.youtube.com/watch?v=AQXIdS1amhM Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28603 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, acute myeloid leukemia, DDX41, myelodysplastic neoplasms, myeloid neoplasms with germline predisposition, R-loop 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. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital 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

Christian Récher, MD, PhD - Practical Considerations for FLT3 Inhibitors in Acute Myeloid Leukaemia: Optimising Our First-Line Approaches With Current and Novel Therapeutics

Christian Récher, MD, PhD - Practical Considerations for FLT3 Inhibitors in Acute Myeloid Leukaemia: Optimising Our First-Line Approaches With Current and Novel Therapeutics

Christian Récher, MD, PhD - Practical Considerations for FLT3 Inhibitors in Acute Myeloid Leukaemia: Optimising Our First-Line Approaches With Current and Novel Therapeutics

Christian Récher, MD, PhD - Practical Considerations for FLT3 Inhibitors in Acute Myeloid Leukaemia: Optimising Our First-Line Approaches With Current and Novel Therapeutics

Christian Récher, MD, PhD - Practical Considerations for FLT3 Inhibitors in Acute Myeloid Leukaemia: Optimising Our First-Line Approaches With Current and Novel Therapeutics

Christian Récher, MD, PhD - Practical Considerations for FLT3 Inhibitors in Acute Myeloid Leukaemia: Optimising Our First-Line Approaches With Current and Novel Therapeutics

Clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of unknown significance (CCUS) are considered precursor diseases to hematologic malignancies,... The post CHIP & CCUS: knowledge gaps, ongoing trials & recommendations for approaching patients with myeloid precursors appeared first on VJHemOnc.

In this episode, we discuss top abstracts in the myeloid space from the American Society of Hematology 2023 meeting with Dr. Anand Patel. Here are the abstracts that were discussed:1. TRANSFORM-1: A Randomized, Double-Blind, Placebo-Controlled, Multicenter, International Phase 3 Study of Navitoclax in Combination with Ruxolitinib Versus Ruxolitinib Plus Placebo in Patients with Untreated Myelofibrosis https://ash.confex.com/ash/2023/webprogram/Paper173509.html 2. MANIFEST-2: Pelabresib in Combination with Ruxolitinib for Janus Kinase Inhibitor Treatment-Naïve Patients with Myelofibrosis: Results of the MANIFEST-2 Randomized, Double-Blind, Phase 3 Study https://ash.confex.com/ash/2023/webprogram/Paper179141.html 3. Venetoclax + Decitabine vs 7+3 in AML https://ashpublications.org/blood/article/142/Supplement%201/970/503790/Comparing-the-Efficacy-and-Safety-of-Venetoclax 4. FILO study: Acute Myeloid Leukemia Patients Who Stopped Venetoclax or/and Azacytidine for Other Reasons Than Progression Have a Prolonged Treatment Free Remission and Overall Survival. https://ash.confex.com/ash/2023/webprogram/Paper185437.html  5. AUGMENT-101: Revumenib Monotherapy in Patients with Relapsed/Refractory KMT2Ar Acute Leukemia: Topline Efficacy and Safety Results https://ash.confex.com/ash/2023/webprogram/Paper172422.html 6. VEN+HMA in HR MDS: Safety, Efficacy, and Patient-Reported Outcomes of Venetoclax in Combination with Azacitidine for the Treatment of Patients with Higher-Risk Myelodysplastic Syndrome: A Phase 1b Study https://ash.confex.com/ash/2020/webprogram/Paper139492.html

Dr. Markku Jalkanen, CEO of Faron Pharmaceuticals Limited, delivered a pivotal presentation on the company's groundbreaking work in cancer treatment, focusing on the reprogramming of myeloid cells to combat cancer at the Proactive One2One Investor Conference. Myeloid cells, originating from bone marrow and exhibiting high plasticity, play a crucial role in cancer, especially in forming tumour-associated macrophages that suppress immunity within tumours. Faron's innovative approach involves reprogramming these cells to support the immune system instead of cancer cells, potentially leading to an immune system attack against cancer cells. The company's leading product, an antibody named Bexmarilimab, demonstrates promising results in controlling tumour environments in solid and haematological cancers. Jalkanen highlighted Bexmarilimab's exceptional safety profile and its ability to convert immunosuppressive macrophages into immune activators. The treatment has shown a significant increase in overall survival rates in cancer patients, particularly in those with no other treatment options. Faron Pharmaceuticals has patent protection until 2037 and has garnered significant interest from big pharma companies. The company is also exploring the potential of Bexmarilimab in treating myeloid leukemia by targeting the Clever-1 molecule on cancerous cells, disrupting their energy production, and reducing their viability. Dr. Jalkanen emphasised the impressive clinical trial results, including a 100% response rate in high-risk myeloid dysplastic syndrome (MDS) patients. The company is now focusing on this patient group, recognising the substantial market opportunity. The trials are ongoing, with expansion plans in the U.S. and Europe. #ProactiveInvestors #FaronPharmaceuticals #CancerResearch #MyeloidCells #CancerTreatment #Bexmarilimab #Immunotherapy #Oncology #MedicalInnovation #DrMarkkuJalkanen #HealthcareTechnology #Pharmaceuticals #TumorResearch #CancerTherapy #LeukemiaTreatment #MedicalResearch #ClinicalTrials #Hematology #BiotechIndustry #CancerBreakthrough #HealthScience #invest #investing #investment #investor #stockmarket #stocks #stock #stockmarketnews

In this week's episode we'll discuss the findings from a natural history study of patients with familial platelet disorder with myeloid malignancy, learn more about the role of HEXIM1 as an essential transcription regulator in human erythropoiesis, and discuss the utility of residual disease as a predictor of relapse in CML patients stopping TKI therapy.

In this episode of the Talking Blood Cancer podcast, host Vanessa is joined by guest Glenys Davidson to share her journey with acute myeloid leukaemia candidly.  Vanessa reflects on the observation of people navigating through treatment at the facility where she is based, setting the stage for a real, raw conversation about the impact of blood cancer on patients and their support networks. Glenys highlights the importance of a positive attitude and familial backing during challenging times, underscoring the emotional and practical support she received from her community. The discussion delves into the specifics of Glenys' treatment, including the physical and emotional toll of chemotherapy, the search for a suitable stem cell donor, and the profound impact of hair loss. The episode also touches on the effects of the COVID-19 pandemic, which impacted treatment procedures and visitation protocols. Further, Glenys emphasises the significance of robust support services for patients and the need for healthcare facilities to communicate the availability of such resources effectively. The conversation concludes with Glenys stressing the importance of social interaction and the realisation of the power of communication during difficult times. The Talking Blood Cancer Podcast is brought to you by the Leukaemia Foundation and is a proud member of the Talking HealthTech Podcast Network - the premier audio destination for cutting-edge insights and thought leadership in healthcare delivery, innovation, digital health, healthcare ICT, and commercialisation. Learn more at www.talkinghealthtech.com/podcast/network

If you're looking to improve your circulation / blood flow and athletic performance or simply combat increased vascular permeability (which can create edema and, therefore, hypoxia) due to the damaging effects of hyperglycemia, inflammation, toxins, etc..., then this episode is a MUST-listen! We're delving into the intricacies of the vesugen bioregulator peptide – so stay tuned for some pretty intriguing research! Topics: 1. Introduction to the Episode - Previous background interest in vesugen: Lyme and Mold / CIRS issues - Introduction to bioregulator peptide vesugen - Effects on blood vessels, circulation, hypoxia, and athletic performance 2. Quick Overview of CIRS and the Circulatory System - Damage to the endothelial blood vessel wall due to high MMP-9 levels - Hemolysins released by MARCoNS - Narrowed capillaries and induced hypoxia - Interest in vesugen 3. Blood Cell Formation - Hematopoiesis - Process and origin in the bone marrow - Characteristics of multipotent hematopoietic stem cells (HSCs) - Regulation of HSC self-renewal vs. differentiation - Myeloid and Lymphoid Progenitors - Differentiated blood cells from each progenitor type - Pathway: Myeloid progenitor to erythrocyte - Role of Erythropoietin (EPO) 4. Maturation Process of Erythrocytes - Ejection of nucleus and organelles - Hemoglobin acquisition - Biconcave shape for optimal gas exchange - Transition to the bloodstream via sinusoids 5. Vascular Wall Anatomy and Dysfunction - Overview of vascular wall layers: Tunica intima, tunica media, and tunica externa - Detailed understanding of endothelial cell functions - Barrier function and vascular permeability - Vascular tone and blood flow regulation - Inflammation and the role in immune response - Angiogenesis and its significance 6. Bioregulator Peptide Vesugen - Definition and unique characteristics - Composition: Lysine, Glutamine, and Asparagine - Mechanism of action: Promotion of endothelial cell proliferation 7. Benefits and Potential of Vesugen - Restoration of endothelial function - Role in injury and endothelial dysfunction scenarios: edema, hypoxia, etc... - Protective effect on the blood-brain barrier - Impact on nitric oxide production and athletic performance, hair growth, skin health Thanks so much for tuning in! Pre-Order Chloe's Book "⁠⁠75 Gut-Healing Strategies & Biohacks⁠⁠" and email thesynthesisofwellness@gmail.com a screenshot of the order confirmation to enter the GIVEAWAY! 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

Learn how the pandemic has helped transform RNA as a platform for oncology drug development in this week's episode. We'll be chatting with Myeloid Therapeutics, who are using RNA technology to direct myeloid cells to harness the innate and adaptive immune system for anti-tumour activity.

In this week's episode, we'll discuss pembrolizumab after autologous stem cell transplantation in patients with peripheral T-cell lymphoma. Newly reported phase 2 study results show that blocking PD-1 with pembrolizumab had a favorable safety profile and demonstrated promising activity, supporting further confirmatory studies in this setting; germline genetic predisposition to myeloid neoplasms in patients with hypoplastic bone marrow. Researchers report mutations that are significantly associated with cytopenias in adulthood in these patients. And pathogenic or likely pathogenic variants were linked to severe cytopenias and advanced myeloid malignancies; and finally, if monocytes and their descendants are less plastic than previously thought. Investigators have identified four functionally specialized monocyte subsets that derive from specific myeloid progenitor lineages. They show that the fate of these monocyte subsets is epigenetically scripted, with little flexibility after differentiation begins, even under conditions of stress.

In this week's episode, we'll learn more about ventricular arrhythmias in sickle cell anemia, discuss the molecular heterogeneity of pediatric monomorphic post–solid organ transplant lymphoproliferative disorders, and uncover the role of the bone marrow microenvironment as a driver of myeloid disorders.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.28.550550v1?rss=1 Authors: Andrews, T. S., Nakib, D., Perciani, C., Ma, X. Z., Liu, L., Winter, E., Camat, D., Chung, S., Manuel, J., Mangroo, S., Hansen, B., Arpinder, B., Thoeni, C., Sayed, B., Feld, J., Gehring, A., Gulamhusein, A., Hirschfield, G. M., Rciutto, A., Bader, G. D., McGilvray, I. D., MacParland, S. A. Abstract: Background: Primary sclerosing cholangitis (PSC) is a serious immune-mediated cholestatic liver disease characterized by bile retention, biliary tree destruction, and progressive fibrosis leading to end stage liver disease and transplantation. There is an unmet need to understand the cellular composition of the PSC liver and how it underlies disease pathogenesis. As such, we generated a comprehensive atlas of the PSC liver and a reference healthy liver dataset using multiple multi-omic modalities with functional validation. Methods: In this work, we employed single-cell (12,000 cells), single-nuclei (23,000 nuclei) and spatial transcriptomics (1 sample by 10x Visium and 3 samples with multi-region profiling by Nanostring GeoMx DSP) to profile the cellular ecosystem in 5 patients with PSC. Transcriptomic profiles were compared to 100k single cell transcriptomes and spatial transcriptomics controls from 24 healthy neurologically deceased donor (NDD) livers. Flow cytometry and intracellular cytokine staining was performed to validate PSC-specific differences in immune phenotype and function. Results: PSC explants with cirrhosis of the liver parenchyma and prominent periductal fibrosis were associated with a unique population of hepatocytes which transformed to a cholangiocyte-like phenotype. Those hepatocytes were surrounded by diverse immune cell populations, including monocyte-like macrophages, liver-resident and circulating natural killer (NK) cells. Cytokines released by inflamed cholangiocytes and fibrosis-resident hepatic stellate cells and endothelial cells recruited CD4+T-cells, dendritic cells, and neutrophils to PSC liver tissues. Tissue-resident macrophages, by contrast, were reduced in number and exhibited a dysfunctional inflammatory response to LPS and IFN-{gamma} stimulation. Conclusions: We present the first comprehensive atlas of the PSC liver and demonstrate hyper-activation and exhaustion-like phenotypes of myeloid cells and markers of chronic cytokine expression in late-stage PSC lesions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this week's episode we'll report on the findings from a 5-year follow-up study of axicabtagene ciloleucel in refractory large B-cell lymphoma, discuss the role of C1 inhibitor deficiency in coagulation and venous thrombosis, and learn how chemotherapy signatures can be used to track the evolution of therapy-related myeloid neoplasms.

In this episode of the IJGC podcast, Editor-in-Chief, Dr. Pedro Ramirez, is joined by Dr. Giuseppe Caruso discuss post-PARP myeloid neoplasms. Dr. Caruso is a fifth-year resident in Obstetrics and Gynecology and a first-year fellow of the PhD in “Network Oncology and Precision Medicine” at Sapienza University of Rome in Italy. Over the past year, he has been attending the Department of Gynecologic Oncology at the European Institution of Oncology (Milan) under the mentorship of Professor Nicoletta Colombo and has now started his research fellowship period at Mayo Clinic (Rochester) under the supervision of Professor William Cliby. His main interest areas are gynecologic oncology, personalized oncology, and clinical research. Highlights: - Myeloid neoplasms post PARPi in patients with ovarian cancer are gradually emerging as life-threatening late toxicities and should not be underestimated. - The first two years of PARPi exposure are the critical window of onset and persistent cytopenia has been recognized as an early warning sign. - Active surveillance, differential diagnosis, and prompt hematological referral are crucial. - PARPi are recommended in the first line also to improve the risk-benefit ratio. - PARPi should be used cautiously in patients with a higher baseline risk and/or those who are less likely to have a significant benefit.

1.     Phase III ASAP trialhttps://ash.confex.com/ash/2022/webprogram/Paper159962.html  2.     Phase III Dauno-Double Trialhttps://ash.confex.com/ash/2022/webprogram/Paper157126.html  3.     Reduced venetoclax exposure: https://ash.confex.com/ash/2022/webprogram/Paper165464.html  4.    Menin Inhibitors in AML https://ash.confex.com/ash/2022/webprogram/Paper164849.htmlhttps://ash.confex.com/ash/2022/webprogram/Paper167412.html  5.    Imetelstat in MDS: IMerge Phase 2https://ash.confex.com/ash/2022/webprogram/Paper169050.html  6.    MOMENTUM: Momelotinibhttps://ash.confex.com/ash/2022/webprogram/Paper162783.htmlHow I manage anemia related to myelofibrosis and its treatment regimens https://link.springer.com/article/10.1007/s00277-023-05126-4

In this week's episode, we'll discuss the safety and efficacy of itacitinib monotherapy in low-risk acute GVHD, learn how ERG was discovered to be a key transcriptional target in EVI1-driven AML, and define a unique subtype of myeloid neoplasms characterized by germline DDX41 mutations.

References J Cancer Res Clin Oncol. 2018; 144(6): 1065–1077 Nature Reviews Drug Discovery. Sep2014, Vol. 13 Issue 9, p673-691 Anal Cell Pathol (Amst). 2018; 2018: 787.1814 The Journal of Biological Chemistry 16/2/2018 293: 2422-2437. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

References The Journal of Biological Chemistry16/2/2018293: 2422-2437. Anal Cell Pathol (Amst). 2018; 2018: 787.1814 Nature Reviews Drug Discovery. Sep2014, Vol. 13 Issue 9, p673-691 J Cancer Res Clin Oncol. 2018; 144(6): 1065–1077. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message

CTLA-4 was a breakthrough; PD-1—a blockbuster, then IDO got busted and biotech retreated to the bench. It got quiet for a while, but the basic science bounced back, and now we have LAG-3, and on the horizon, a new VISTA. Myeloid cells have the target, and Sensei Bio has the drug. Tune in as CEO John Celebi tells us the story of SNS-101 and why the Fc component is so important.

A new review was published in Oncotarget's Volume 13 on November 17, 2022, entitled, “Myeloid-derived suppressor cells: Cancer, autoimmune diseases, and more.” Although cancer immunotherapy using immune checkpoint inhibitors (ICIs) has been recognized as one of the major treatment modalities for malignant diseases, the clinical outcome is not uniform in all cancer patients. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells that possess various strong immunosuppressive activities involving multiple immunocompetent cells that are significantly accumulated in patients who did not respond well to cancer immunotherapies. In this new review paper, researchers Masahiko Shibata, Kotaro Nanno, Daigo Yoshimori, Takahiro Nakajima, Makoto Takada, Takashi Yazawa, Kousaku Mimura, Norio Inoue, Takafumi Watanabe, Kazunoshin Tachibana, Satoshi Muto, Tomoyuki Momma, Yoshiyuki Suzuki, Koji Kono, Shungo Endo, and Seiichi Takenoshita from Fukushima Medical University, Aizu Chuo Hospital, Aizu Oncology Consortium, Nippon Medical School, and Bange Kousei General Hospital reviewed the perspective of MDSCs with emerging evidence. “Here, we review the following: the phenotypes and origins of MDSCs; the mechanisms of immunosuppression by MDSCs; MDSC functions in the TME; MDSCs in benign disorders and physiology; and consideration of MDSC manipulation in cancer treatment.” Many studies on MDSCs were performed in malignant diseases. Substantial studies on the participation of MDSCs on non-malignant diseases such as chronic infection and autoimmune diseases, and physiological roles in obesity, aging, pregnancy and neonates have yet to be reported. With the growing understanding of the roles of MDSCs, variable therapeutic strategies and agents targeting MDSCs are being investigated, some of which have been used in clinical trials. More studies are required in order to develop more effective strategies against MDSCs. ICI therapies have been developed and demonstrated surprising outcomes in many types of cancer. However, the effects of ICIs are not universal or uniformal in all cancer patients, and emerging evidence has indicated that MDSCs are a crucial target to overcome this important issue with a growing understanding of the roles of MDSCs, variable therapeutic strategies and agents targeting MDSCs are under exploration, some of which have been used in clinical trials. “More studies are required for the development of more effective strategies against MDSCs.” DOI: https://doi.org/10.18632/oncotarget.28303 Correspondence to: Masahiko Shibata - mshibata@fmu.ac.jp Video: https://youtu.be/ZJj6CzcJ6x4 Keywords: MDSC, immunosuppression, Treg, TAM, cancer 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, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.

BARCELONA, Spain—Liquid biopsies are increasingly used to identify cancer progression and could also provide molecular evidence of higher risk for hematologic malignancies and solid tumors, according to findings from a study of circulating tumor DNA reported at the European Organization for Research and Treatment of Cancer—National Cancer Institute—American Association for Cancer Research (EORTC-NCI-AACR) 2022 Symposium on Molecular Targets and Cancer Therapeutics. Marco Tagliamento, PhD student, medical oncologist, and research fellow at the Gustave Roussy Institute, France, told the symposium about study findings from the large Gustave Roussy Molecular Tumor Board dataset able to identify genetic mutations involved in clonal hematopoiesis. Tagliamento told the conference 113 patients—8 percent of their total—were found to have had at least one clonal hematopoiesis mutation that could be considered to place them at higher risk of developing hematologic malignancies. “Out of these patients, 45 were referred to our hematology unit by their oncologist and five were subsequently diagnosed with blood cancer: one with myelomonocytic leukemia, two with myelodysplastic syndrome and two with essential thrombocythemia,” Tagliamento told the symposium. Journalist Peter Goodwin briefly interviewed Tagliamento on his findings at EORTC-NCI-AACR.

In this week's episode we will review data showing that lenalidomide promotes development of TP53-mutated, therapy-related myeloid neoplasms. Next, we'll discuss the first prospective study to evaluate abnormal uterine bleeding in women starting anticoagulation for venous thromboembolism. Lastly, we'll review an optimized tri-specific antibody that overcomes immune escape and enhances therapeutic efficacy in a patient-derived xenograft model of B-cell ALL.

Listen to a soundcast of the 8/24/22 and 8/26/22 FDA approvals of Imbruvica (ibrutinib) for pediatric patients with chronic graft versus host disease, including a new oral suspension, and Pemazyre (pemigatinib) for relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement.”

Dr Patel discusses post-transplant complications in myeloid disorders, the prevalence of these complications, and the most common ones that may arise, including primary disease relapse, graft-vs-host disease, infection, organ toxicity, persistent cytopenias, and immunosuppression.

Dr Verstovsek discusses the FDA approval of pemigatinib in myeloid/lymphoid neoplasms with FGFR1 rearrangements, the transformative effects of pemigatinib, and the importance of identifying chromosomal abnormalities in patients with this aggressive disease.

Personalised Management of Newly Diagnosed Secondary Acute Myeloid Leukaemia: Determining Factors That Impact Treatment Decisions

Personalised Management of Newly Diagnosed Secondary Acute Myeloid Leukaemia: Determining Factors That Impact Treatment Decisions

Personalised Management of Newly Diagnosed Secondary Acute Myeloid Leukaemia: Determining Factors That Impact Treatment Decisions

Personalised Management of Newly Diagnosed Secondary Acute Myeloid Leukaemia: Determining Factors That Impact Treatment Decisions

In this week's episode, we'll learn more about neuropsychiatric manifestations and stroke risk in hereditary TTP, discuss germline DDX41 variants as predisposing factors to myeloid neoplasms, and learn more about the prognostic impact of DDX41 mutations in adults with intensively treated AML.

Hear about a new treatment that may be able to reverse hearing loss, how new solar energy storage technology could eventually power our phones, and the surprisingly grand history of chickens.Reversing hearing loss. “Reversing hearing loss with regenerative therapy” by Zach Winnhttps://news.mit.edu/2022/frequency-therapeutics-hearing-regeneration-0329“What are Progenitor Cells? Exploring Neural, Myeloid and Hematopoietic Progenitor Cells” by Nicole Gleichmannhttps://www.technologynetworks.com/cell-science/articles/what-are-progenitor-cells-exploring-neural-myeloid-and-hematopoietic-progenitor-cells-329519“Quick Statistics About Hearing” by the National Institute on Deafness and Other Communication Disordershttps://www.nidcd.nih.gov/health/statistics/quick-statistics-hearing“PCA Approach” and “About Hearing Loss” by Frequency Therapeuticshttps://www.frequencytx.com/science/pca-approach/https://www.frequencytx.com/hearing-loss/about-hearing-loss/“FX-322 in Adults With Acquired Sensorineural Hearing Loss” by Frequency Therapeutics Clinical Trialhttps://clinicaltrials.gov/ct2/show/NCT05086276Phone charger, but make it the sun.“Converting solar energy to electricity on demand” by Chalmers University of Technologyhttps://techxplore.com/news/2022-04-solar-energy-electricity-demand.html“For a Better Future” by The MOST Solar Projecthttps://mostsolarproject.eu/“Molecular solar thermal (MOST) energy storage and release system” by Kasper Moth-Poulsen, et al.https://pubs.rsc.org/en/content/articlelanding/2012/ee/c2ee22426g“Solar Energy: Benefits and Drawbacks” by Matthew Johnstonhttps://www.investopedia.com/articles/investing/053015/pros-and-cons-solar-energy.aspChicken breeding.“The biocultural origins and dispersal of domestic chickens” by Joris Peters, Ophélie Lebrasseur, Evan K. Irving-Pease, Ptolemaios Dimitrios Paxinos, Julia Best, Riley Smallman, Cécile Callou, Armelle Gardeisen, Simon Trixl, Laurent Frantz, Naomi Sykes, Dorian Q. Fuller, and Greger Larson.https://www.pnas.org/doi/full/10.1073/pnas.2121978119“A new origin story for domesticated chickens starts in rice fields 3,500 years ago” by Bruce Bower.https://www.sciencenews.org/article/chicken-domestication-bones-origin-asia-rice-fields-exotic-animals“Redefining the timing and circumstances of the chicken's introduction to Europe and north-west Africa” by Julia Best, Sean Doherty, Ian Armit, Zlatozar Boev, Lindsey Büster, Barry Cunliffe, Alison Foster, Ben Frimet, Sheila Hamilton-Dyer, Tom Higham, Ophélie Lebrasseur, Holly Miller, Joris Peters, Michaël Seigle, Caroline Skelton, Rob Symmons, Richard Thomas, Angela Trentacoste, Mark Maltby, Greger Larson, and Naomi Sykeshttps://www.cambridge.org/core/journals/antiquity/article/redefining-the-timing-and-circumstances-of-the-chickens-introduction-to-europe-and-northwest-africa/0797DAA570D51D988B0514C37C2EC534Follow Curiosity Daily on your favorite podcast app to get smarter with Calli and Nate — for free! Still curious? Get exclusive science shows, nature documentaries, and more real-life entertainment on discovery+! Go to https://discoveryplus.com/curiosity to start your 7-day free trial. discovery+ is currently only available for US subscribers.Find episode transcripts here: https://curiosity-daily-4e53644e.simplecast.com/episodes/healing-hearing-hairs-sun-phones-chicken-gods

A pastor named Dave had been fighting Acute Myeloid Leukemia for a while and all signs were pointing up that he was going to beat this but then something tragic happened. His appendix ended up rupturing and because of that, he was in some real trouble. The cancer had destroyed all of his white blood cells which prevented him from fighting off any sort of infection.But just as the doctors and members of his church were losing hope of him beating this, one lady at his church said something that stuck with him. 

Dr. Stephen Ansell, of the Mayo Clinic in Minnesota, tells host Dr. John Sweetenham, of the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, about ECHELON-1's compelling overall survival analysis in newly diagnosed Hodgkin lymphoma and key advances in the SHINE, MOMENTUM, and ASCEMBL trials that were featured at the 2022 ASCO Annual Meeting.   TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the associate director for Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and host of the ASCO Daily News Podcast.  My guest today is Dr. Stephen Ansell, a professor and chair of medicine at the Department of Hematology at the Mayo Clinic in Minnesota. Dr. Ansell shares his insights on key advances in hematologic malignancies that were featured at the 2022 ASCO Annual Meeting.  Our full disclosures are available in the show notes and disclosures of all guests on podcasts can be found on our transcripts at asco.org/podcasts.   Stephen, it's great to have you on the podcast today.  Dr. Stephen Ansell: Thanks so much for having me, John.  Dr. John Sweetenham: So, Stephen, I'd like to start with your thoughts on Abstract 7503, which of course is one that you authored, and this is a 6-year follow-up study of the ECHELON-1 trial. This includes a positive overall survival analysis for brentuximab vedotin in newly diagnosed advanced Hodgkin lymphoma. Can you tell us more about this?  Dr. Stephen Ansell: Yeah, sure, John. And you know, as you point out, the thing that's really interesting and unique about this trial is we haven't had a lot of studies in Hodgkin lymphoma that show an overall survival advantage as you well know. Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy has actually been quite difficult to beat when it's been an overall survival endpoint that one has been looking at.  There have been some other strategies in the past that have been looked at—the escalation of therapies such as escalator BEACOPP, and maybe modification of therapy to minimize toxicity, such as the RATHL trial where bleomycin is dropped out.  In all of these studies, there have been advantages for progression-free survival, but not clearly against ABVD as the standard and overall survival advantage. So, our listeners would probably know that ECHELON-1 was a comparison between brentuximab vedotin ABVD chemotherapy, and ABVD chemotherapy as the standard, showing an initially modified progression-free survival advantage and subsequently a progression-free survival advantage. But now with 6 years of follow-up, an overall survival advantage. And I think that's really what makes this quite unique.  Dr. John Sweetenham: One of the reasons I think many people, myself included, thought that it was going to be a very high bar to show an overall survival difference in this study was simply the fact that treatments to relapsed and refractory Hodgkin lymphoma, in general, have improved really quite substantially, both before and during the conduct of this trial.  Do you have any thoughts on that? Were you surprised? And any thoughts on why we're seeing this in the face of the rapidly evolving treatment landscape in the relapse setting?  Dr. Stephen Ansell: Yeah, I think that's an excellent point. And, John, I think there have been 2 schools of thought, as you know, those that have felt that the first shot was always the best one. And you should go hard right off the bat and others have said, you don't need to give everybody intensive treatment, because as you say, subsequent therapies can be very effective.  This would actually challenge that second position because when we looked at how patients were managed in both groups when they relapsed, the vast majority of relapsing patients in the group that got ABVD subsequently got brentuximab vedotin, as part of their regimen. Most patients—and it was balanced in both arms—got the standard kind of salvage treatment, autologous stem cell transplant approach, and some patients in both arms, got novel agents, including PD1 blockade, that was a minority, partly because of the timing of when the study was done.  But I think all of the things that we would normally do were done, and yet there's still a survival advantage. The one interesting thing I think that's worth taking away from this is when one looked at some of the influences on what might have made that overall survival difference, there were more patients progressing and dying from Hodgkin's in the ABVD arm suggesting that adding brentuximab vedotin does make a difference to the disease itself. But also interestingly, there were fewer patients in the brentuximab arm, who got a second lymphoma.  And interestingly, there were quite a substantial number of people in the ABVD arm when they relapsed to or subsequently got a different lymphoma, suggesting that the brentuximab vedotin, may actually target a precursor cell in a heme malignancies space and actually may have a benefit that way.  Dr. John Sweetenham: So, what's your overall conclusion from this study now that brentuximab vedotin plus ABVD is the standard of care for patients with newly diagnosed advanced Hodgkin lymphoma?  Dr. Stephen Ansell: I would say that if you have advanced-stage disease with classical Hodgkin lymphoma histology, it's very difficult not to say that this would be the standard of care to manage the patients.  I think we've learned that this study applied to older patients who are often difficult to treat. And so, hence, that's also a very valid treatment to give. And it's very difficult to argue against giving treatment that has an overall survival advantage for patients. So, in my practice, this has become the standard of care.  Dr. John Sweetenham: Okay, great. Thanks, Stephen. Let's move on and talk about LBA7502. This reported on the primary results of a double-blind placebo-controlled study known as SHINE, which looks at the use of ibrutinib in combination with bendamustine and rituximab followed by rituximab maintenance as a first-line treatment for older patients with mantle cell lymphoma. What are your thoughts and key takeaways from this study?  Dr. Stephen Ansell: Again, I think this is a very important study in older patients with mantle cell lymphoma. So, as you well know and many of our listening audience would know that we kind of has 2 strategies in mantle cell lymphoma. In younger patients, we may treat them with a more intense approach, sometimes with autologous stem cell transplant, often with a kind of alternating high-intensity therapies.  For patients who are older, bendamustine rituximab is really a standard therapy for patients with that demographic. And this now really pushes the field forward by showing that if you take bendamustine rituximab and add ibrutinib an effective therapy in the relapse setting, in the upfront setting, there is a substantial advantage for how patients do.  If one looks at the overall outcomes, it shows that progression-free survival is improved; we don't have overall survival benefit yet. But as we track these patients, it'll be interesting to see if that does transpire in time.  I will say again that I always like placebo-controlled arms because it helps us really get a handle on toxicities. And in general, in this population of patients, it was well tolerated. So, I think this, again, is a regimen that is going to be very useful in older patients.  Dr. John Sweetenham: I think that the lack of an overall survival benefit so far could of course be because there was a crossover in a study for those patients who progressed on the placebo-controlled arm.  But my other question about this, just to get your impression, is that there is a subgroup of elderly patients or older patients with a very slowly progressive disease where the management approach has been more of a watch-and-wait and observation-only approach until they become symptomatic. Do you think results like this, which start to show a progression-free survival benefit from upfront therapy, change that philosophy? Should we be thinking harder about whether anyone should be observed now?  Dr. Stephen Ansell: I think that's a good question. And to be frank, I will say that in my practice, I still have a spirit of, I'm happy to watch patients who have a very low burden of disease to just get a sense of the pace of the disease. Because as you say, you may be surprised by a subset of patients whom you may not need to treat for a year or even longer. And my view is that a year of no treatment is always better than a prolonged progression-free survival interval on treatment. So, I take the view that if you don't need to treat, that is still the best management.  Dr. John Sweetenham: Great, thank you! So, we're going to change gear for a moment and move out of lymphoid malignancy and talk a little about Myeloproliferative Syndrome. I'm interested to hear your thoughts on the MOMENTUM study. So, this was Abstract 7002, another phase 3 randomized study, in this case, looking at the use of momelotinib versus danazol in symptomatic and anemic patients with Myelofibrosis, who previously had a JAK inhibitor. What are your thoughts on this study?  Dr. Stephen Ansell: I think again, this is really good and very interesting data because those that treat Myelofibrosis will know these are challenging to treat. And many times, the symptoms they experience, the transfusion challenges they have, and the difficulty they have with very large spleens are all things that impact the quality of life quite profoundly. And therapies, in general, that would benefit those symptoms are always highly valuable.  So, I did find, again, I'm not as much of an expert in Myelofibrosis, but certainly, my colleagues who are were very satisfied with these results, basically showing improvement when compared to danazol, which again, I would anticipate as modest control with not particularly good efficacy, again, some of those symptoms I just spoke about, but momelotinib really showed a substantial benefit for the symptoms that this disease causes, and obviously transfusion requirements and improved spleen sizes and spleen symptoms.  So, I think in general, for managing patients for whom the quality of life is profoundly impacted, this is going to be a useful agent moving forward.  Dr. John Sweetenham: Okay, great. Thanks. And staying on the theme of Myeloid diseases, Abstract 7004 reported on the efficacy and safety, from the so-called ASCEMBL study, another phase 3 study, in this case, looking at the use of asciminib versus bosutinib in patients with Chronic Myeloid Leukemia (CML) who are in chronic phase, and who had already received 2 or more tyrosine kinase inhibitors. And this was an update at week 56 of the study. Why do you think this study should be on our radar?  Dr. Stephen Ansell: Well, I think again, we're always looking for agents that make a difference, particularly with subsequent lines of therapy in this disease. I think bosutinib is really regarded as a standard of care in this population of patients and an agent that comes along, ascitinib in this case, that shows a significant benefit, that really brings yet another tool for us to utilize in these patients.  I must say, again, as I looked at the results, comparing also looking for the major molecular responses, and the benefit and durability thereof, this was pretty impressive data. And so, I think it's very useful in this disease to have a plethora of tools that we can reach to be able to really impact the outcome of patients. So, I think, again, this is highly relevant data that we would use in the clinic in the not-distant future.  Dr. John Sweetenham: Do you think it's likely it'll move into frontline treatment over time?  Dr. Stephen Ansell: So, I think that is a good question. I don't know the answer to that, except to say that these results are pretty impressive. And so, I do believe that that's going to need to be tested, but as has been done in CML over the decades and which is really to be applauded, there have been randomized trials, comparing head-to-head agents showing which agent really has the greatest benefit and efficacy. So, I'll watch that space with a lot of interest.  Dr. John Sweetenham: Thanks! And finally, I'd like to return to lymphoid malignancy. In the 2020s, it would be almost impossible to review a meeting such as ASCO without saying something about CAR T-cell therapy, and this podcast is going to be no exception.  So, I wonder if I could get your thoughts on Abstract 7571. And this was an abstract, which reported real-world outcomes for axicabtagene ciloleucel, otherwise known as the Axi-Cel, for the treatment of large B-cell lymphoma. And it looked at the outcomes according to race and ethnicity. What are your thoughts on this study?  Dr. Stephen Ansell: Well, John, I smiled when you were said there's not a possible to really have a conversation without bringing in CAR T-cell somewhere along the way, but what I liked about this abstract, is it really was bringing in the real-world data, because many times and again, I have to stress that real-world data, when it comes to CAR T-cells is probably not the real world in the most real-world nature of things. And that is just you have to have access to certain centers to be able to get this therapy. And I think that's what this abstract actually points to.  It does look at almost 1,400 patients treated with Axi-Cel. And now that in large cell lymphoma, this is a standard of care where we either use a post-transplant and now even as a first relapse therapy, this is becoming highly relevant. And the question is just always seeing discrepancies between various population groups when we look at how outcomes transpire from this therapy.  And as it turns out, if one looks at Asian populations, those are really not adversely impacted, or Hispanic populations. But the African American population continues to have a less favorable outcome, even with this sophisticated therapy.  And that does suggest that possibly, when those patients, in general, can get access to this care, might actually be a little later in the disease, greater disease burden, possibly a little later line of therapy, resulting in not as favorable results.  I think this is whereas health care providers, we need to turn our attention in the future. And that is to say, how can we make care be equally good for all patients everywhere within our country, rather than there being nuggets where certain people benefit a lot and other areas where people benefit very little.  Dr. John Sweetenham: Yeah, thank you. There was good discussion after this study was presented and I think much of it focused around exactly what you've just said. Most of this difference is almost certainly not biological but it's really related to access to care and so on and that was an important take-home message. So, thanks for emphasizing that.  Stephen, thanks so much for sharing your insights with us today regarding the 2022 ASCO Annual Meeting on our podcast. I really appreciate your being willing to talk to us.  Dr. Stephen Ansell: John, thank you very much for having me.  Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstract discussed today on the transcripts 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.    Disclosures:  Dr. John Sweetenham:  Consulting or Advisory Role: EMA Wellness  Dr. Stephen Ansell:  Honoraria: WebMD, Research to Practice  Research Funding (Inst.): Bristol-Myers Squibb, Seattle Genetics, Affimed Therapeutics, Regeneron, Trillium Therapeutics, AI Therapeutics, ADC Therapeutics  Disclaimer:  The purpose of this podcast is to educate and 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.       

The Scientist is bringing you a new podcast series of special edition episodes! Get a sneak peek here and subscribe to the The Scientist's LabTalk channel for access to additional science stories.   The Scientist's LabTalk podcast is produced by The Scientist's Creative Services Team. We explore topics at the leading edge of innovative research. This episode is brought to you by Keystone Symposia. Don't miss their upcoming virtual eSymposium on myeloid cells and innate immunity in solid tumors on September 21-23, 2020. Find more information at http://keysym.us/Myeloid21Scientist One of the eSymposium's speakers is Miriam Merad, a professor in Cancer Immunology and the Director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai. Niki Spahich from The Scientist's Creative Services team spoke with Merad about her research investigating how antigen presenting cells enhance anti-tumor immune responses and her recent advocacy work fighting against the foreign scholar visa ban.  

Welcome to The Scientist's LabTalk, a special edition podcast produced by The Scientist's Creative Services Team where we explore topics at the leading edge of innovative research. This episode is brought to you by Keystone Symposia. Don't miss their upcoming virtual eSymposium on myeloid cells and innate immunity in solid tumors on September 21-23, 2020. http://keysym.us/Myeloid21Scientist One of the eSymposium's speakers is Miriam Merad, a professor in Cancer immunology and the Director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai. Niki Spahich from The Scientist's Creative Services team spoke with Merad about her research investigating how antigen presenting cells enhance anti-tumor immune responses, and her recent advocacy work fighting against the foreign scholar visa ban.