Podcasts about hematologic malignancies

Listen in as Jonathan A. Bernstein, MD, and Ryan Haumschild, PharmD, MS, MBA, CPEL, discuss how to manage the multidisciplinary care of patients with systemic mastocytosis (SM) from both the allergy/immunology and pharmacy perspective, including:Strategies to better identify patients presenting with features of SM to facilitate timely diagnosisCurrent guideline-recommended treatment approachesEmerging data on new targeted agents for SMPharmacist-led strategies to help patients achieve better outcomes (e.g., specialist referral, polypharmacy counseling, and anaphylaxis education)PresentersJonathan A. Bernstein, MDProfessor of MedicineDivision of Rheumatology, Allergy and ImmunologyDepartment of Internal MedicineUniversity of Cincinnati College of MedicinePartner Advanced Allergy Services, LLCPartner Bernstein Clinical Research Center, LLCCincinnati, OhioRyan Haumschild, PharmD, MS, MBA, CPELVice President of Pharmacy, AmbulatoryEmory HealthcareWinship Cancer InstituteAtlanta, GeorgiaFull link to program page:https://bit.ly/3HcA8z2

CancerNetwork® visited Sibley Memorial Hospital of Johns Hopkins Medicine to speak with a variety of experts about therapeutic advancements and ongoing research initiatives across several different cancer fields. As part of each discussion, clinicians highlighted how collaboration across different departments has positively impacted treatment planning, decision-making, and outcomes at their institution. These experts included the following: ·      Rachit Kumar, MD, an assistant professor of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins School of Medicine and a radiation oncologist specializing in genitourinary and gastrointestinal cancers at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center for Sibley Memorial Hospital and Suburban Hospital; ·      Michael J. Pishvaian, MD, PhD, director of Gastrointestinal, Developmental Therapeutics, and Clinical Research Programs, and associate professor of Oncology at Johns Hopkins School of Medicine; ·      Nina Wagner-Johnston, MD, a professor of Oncology and the director of Lymphoma Drug Development at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, director of Hematologic Malignancies National Capital Region, and co-director of Clinical Research for Hematologic Malignancies; ·      Valerie Lee, MD, an assistant professor of Oncology at Johns Hopkins University School of Medicine and a medical oncologist at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center at Sibley Memorial Hospital; ·      Armine Smith, MD, the director of urologic oncology at the Sidney Kimmel Comprehensive Cancer Center at Sibley Memorial Hospital, and an assistant clinical professor of Urology at the Brady Urological Institute of Johns Hopkins University School of Medicine; ·      Pouneh Razavi, MD, the director for Breast Imaging in the National Capital Region and an instructor in Radiology and Radiological Science; ·      and Curtiland Deville Jr., MD, medical director of the Johns Hopkins Proton Therapy Center and clinical director of Radiation Oncology at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center at Sibley Memorial Hospital. Altogether, their insights demonstrated how multidisciplinary teamwork has improved outcomes ranging from patient survival to healthcare resource utilization across a wide range of diseases including breast cancer, gastrointestinal cancer, genitourinary cancer, hematologic malignancies, and others.

Darshan H. Brahmbhatt, Podcast Editor of JACC: Advances, discusses a recently published original research paper on Effect of Sacubitril/Valsartan or Enalapril on Left Ventricular Function in Patients With Hematologic Malignancies Treated With Bone Marrow Transplantation: A Randomized Controlled Trial

In this episode of the Bench to Bedside podcast, Dr. Roy Jensen, vice chancellor and director of The University of Kansas Cancer Center, hosts Dr. Marc Hoffmann, associate professor specializing in Hematologic Malignancies and Cellular Therapeutics at the University of Kansas Medical Center and medical director of the lymphoma program at KU Cancer Center, where he also serves as medical director for quality improvement initiatives. Beyond his clinical expertise, Dr. Hoffmann has contributed significantly to research in lymphoma and chronic lymphocytic leukemia (CLL), and he actively participates in national cooperative group clinical trials. Dr. Hoffmann shares his career path into the field of oncology, innovations in lymphoma and CLL treatments, as well as the unique aspects of KU Cancer Center's lymphoma program. The conversation also covers Dr. Hoffmann's Peace Corps experience in West Africa, his involvement in clinical trials, and advice for medical students interested in hematology and oncology. Do you have questions about cancer? Call our Bench to Bedside Hotline at (913) 588-3880 or email us at benchtobedside@kumc.edu, and your comment or question may be shared on an upcoming episode! If you appreciated this episode, please share, rate, subscribe and leave a review. To ensure you get our latest updates, For the latest updates, follow us on the social media channel of your choice by searching for KU Cancer Center. Links from this Episode: Learn more about the lymphoma program at KU Cancer Center Learn about chronic lymphocytic leukemia (CLL) Learn more about CAR T-cell therapy at KU Cancer Center Learn more about Dr. Marc Hoffmann Watch a video of Dr. Hoffmann explaining how blood cancer is diagnosed  

This week, Jonathan is joined by Marc Hoffman, Associate Professor in Hematologic Malignancies and Cellular Therapeutics at the University of Kansas Medical Center, to discuss novel therapies for B-cell malignancies and current challenges in hemato-oncology.   Timestamps:     (00:00)-Introduction  (03:24)-What is molecular biophysics?  (07:01)-Marc's journey into hemato-oncology  (09:36)-Advice to young doctors  (13:08)-Treatment advances in diffuse large B-cell lymphoma   (19:11)-BRUIN study: pirtobrutinib for B-cell malignancies   (26:15)-Challenges in CAR-T therapy implementation  (31:31)-A pharmaceutical perspective   (38:10)-Regulatory insights into clinical trials  (40:58)-New horizons in hemato-oncology  (44:26)-Marc's three wishes for healthcare 

In this podcast episode, Dr. Versha Banerji, a Canadian hematologist from Manitoba and Dr. Jennifer Brown, an internationally renowned hematologist from the United States, discuss data on the treatment of CLL presented at the American Society of Hematology (or ASH) meeting in San Diego, CA. The discussion involves an analysis of the data from 8 presentations on combination and novel therapies for the treatment of CLL. In this discussion, the data is put into the Canadian context, with key take-aways that are relevant to practice in Canada.  Our Guests:Dr. Versha Banerji is a hematologist at Max Rady College of Medicine at the University of Manitoba in Winnipeg, Manitoba.Dr. Jennifer Brown is the Director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute and Professor of Medicine in the Field of Hematologic Oncology at Harvard Medical School in Boston, Massachusetts.This podcast episode was sponsored by BeiGene Canada ULC.If you enjoyed our podcast episode, please review and subscribe. For other medical education content, visit our website at: https://www.impactmedicom.com (https://www.impactmedicom.com/).

Today we are bringing you a conversation on treatment with Bruton tyrosine kinase inhibitors for patients with treatment-naïve chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Ryan Haumschild, PharmD, MS, MBA, CPEL, vice president of ambulatory pharmacy at Emory Healthcare and Winship Cancer Institute, spoke with 3 experts: Tara Graff, DO, medical oncologist, Mission Cancer and Blood; Jacqueline Barrientos, MD, MS, chief, Hematologic Malignancies, and director, Oncology Research at Mount Sinai Comprehensive Cancer Center; and Matthew Davids, MD, MMSc, director of Clinical Research, Division of Lymphoma, Dana-Farber Cancer Institute, and associate professor of medicine, Harvard Medical School. They covered a wide range of topics including the data on treatment regimens for both CLL and MCL, the cost of treatment, patient-specific considerations during treatment decision making, and the future of treatment.

This 30-minute CME-accredited program, hosted by John Kuruvilla, MD, discusses best practices for talking to patients with hematologic malignancies about possibly participating in clinical trials.Jointly Provided by American Academy of CME and CheckRare CE.Support for this accredited continuing education activity has been made possible through educational grant from Merck.Estimated time to complete: 0.5 hours Start date: November 30, 2024End date: November 30, 2025  Activity FacultyJohn Kuruvilla, MDHematologist / Clinical InvestigatorPrincess Margaret Cancer CentreProfessor of MedicineUniversity of Toronto Target AudienceThis activity has been designed to meet the educational needs of physicians specializing in hematology-oncology. Other healthcare providers, including NPs and PAs, may also participate. Learning ObjectivesAfter participating in the activity, learners should be better able to- Describe the importance of clinical trials in furthering the science of hematologic malignancies treatment.- Describe and utilize best practices for engaging patients in shared decision making regarding clinical trial participation. Accreditation and Credit DesignationIn support of improving patient care, this activity has been planned and implemented by American Academy of CME, Inc. and CheckRare CE. American Academy of CME, Inc. 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. PhysiciansAmerican Academy of CME, Inc., designates this enduring material for a maximum of 0.5 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Other HCPsOther members of the care team will receive a certificate of participation. Disclosure StatementAccording to the disclosure policy of the Academy, all faculty, planning committee members, editors, managers and other individuals who are in a position to control content are required to disclose any relationships with any ineligible company(ies). The existence of these relationships is not viewed as implying bias or decreasing the value of the activity. Clinical content has been reviewed for fair balance and scientific objectivity, and all of the relevant financial relationships listed for these individuals have been mitigated.Disclosure of relevant financial relationships are as follows: Faculty Educator/PlannerDr. Kuruvilla discloses the following relevant financial relationships with ineligible companies:Honoraria: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Beigene, Genmab, Gilead Sciences, GlaxoSmithKline, Incyte, Janssen, Karyopharm, Merck, Novartis, Pfizer, Roche, Seattle GeneticsConsultant: AbbVie, Bristol Myers Squibb, Gilead Sciences/Kite, Merck, Roche, Seattle GeneticsGrant/Research Support: AstraZeneca, Kite, Merck, Novartis, RocheData Safety Monitoring Board: KaryopharmPlanners for this activity have no relevant financial relationships with any ineligible companies. This activity will not review off-label or investigational information. The opinions expressed in this educational activity are those of the faculty, and do not represent those of the Academy or CheckRare CE. This activity is intended as a supplement to existing knowledge, published information, and practice guidelines. Learners should appraise the information presented critically, and draw conclusions only after careful consideration of all available scientific information. Method of ParticipationThere are no fees to participate in the activity. Participants must review the activity information including the learning objectives and disclosure statements, as well as the content of the activity. To receive CME credit for your participation, please go to https://checkrare.com/learning/p-hematologic-malignancies-and-clinical-trial-participation-a-shared-decision-making-approach/   PrivacyFor more information about the American Academy of CME privacy policy, please access http://www.academycme.org/privacy.htm  For more information about CheckRare's privacy policy, please access https://checkrare.com/privacy/ContactFor any questions, please contact: CEServices@academycme.org               

Educational Objectives • Review recent clinical updates of RET inhibitors and how they fit into the treatment paradigm for non‒small cell lung cancer • Identify and manage adverse effects of RET inhibitors to ensure patient safety and improve adherence Moderator:  Lauren Ledbetter, PharmD, BCOP Clinical Pharmacy Specialist, Thoracic Medical Oncology The James Cancer Hospital at The Ohio State University Columbus, Ohio Faculty: Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA Clinical Pharmacy Manager University of Kansas  Cancer Center Division of Hematologic Malignancies & Cellular Therapeutics Disclosures Lauren Ledbetter, PharmD, BCOP, has the following financial relationships with commercial interests to disclose: Consultant: The Dedham Group, Charles River Associates Speakers  Bureau: APPOS Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA, has the following financial relationships with commercial interests to disclose: Consultant: Pfizer, Sanofi, Genmab, Janssen Accreditation: Pharmacy Times Continuing Education™ is accredited by the  Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This activity is approved for 0.5 contact hour (0.5 CEU) under the ACPE universal activity number 0290-0000-24-304-H01-P. The activity is available for CE credit  through October 31, 2025. Supporter: This activity is supported by an educational grant from Rigel Pharmaceuticals, Inc.

Educational Objectives Review recent clinical updates of RET inhibitors and how they fit into the treatment paradigm for non‒small cell lung cancer Identify and manage adverse effects of RET inhibitors to ensure patient safety and improve adherence   Faculty Lauren Ledbetter, PharmD, BCOP Clinical Pharmacy Specialist, Thoracic Medical Oncology The James Cancer Hospital at The Ohio State University Columbus, Ohio   Moderator Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA Clinical Pharmacy Manager University of Kansas Cancer Center Division of Hematologic Malignancies & Cellular Therapeutics   Pharmacy Times Continuing Education™ is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This activity is approved for 0.5 contact hour (0.05 CEU) under the ACPE universal activity number 0290-0000-24-304-H01-P. The activity is available for CE credit through October 31, 2025.   This activity is supported by an educational grant from Rigel Pharmaceuticals, Inc.

This episode of ASTCT Talks dives into outpatient CAR T therapy, exploring logistics, challenges, and success strategies. Host Dr. Zahra Mahmoudjafari leads a panel of experts to share insights from their innovative programs. The panel features Robb Richards, Administrative Director of Cell Therapy and Transplant at Penn Medicine; Dr. Katie Gatwood, Clinical Pharmacy Specialist at Vanderbilt University Medical Center; and Dr. Taha Al-Juhaishi, Associate Director at the University of Oklahoma's Transplant and Cell Therapy Program. Topics include outpatient program structures, toxicity management, and the evolving role of cell therapies beyond hematologic malignancies. About the Host:Dr. Zahra Mahmoudjafari is a board-certified oncology pharmacist and Clinical Pharmacy Manager in Hematologic Malignancies at the University of Kansas Cancer Center. She earned her PharmD and MBA from UMKC and focuses on clinical and operational management of cell and gene therapies. Dr. Mahmoudjafari is active in HOPA, ATOPP, and ASTCT and was honored with ASTCT's Pharmacy SIG Lifetime Achievement Award and ASCO's 40 Under 40 in Cancer Award. Meet the Panel: Robb Richards has over 20 years of oncology experience, with roles spanning private practice, IT, and leadership in healthcare systems. At Penn Medicine, he oversees CAR T therapy operations, expanding services into community hospitals. He holds degrees from Drexel University and St. Joseph's University. Dr. Katie Gatwood is a Board-Certified Oncology Pharmacist at Vanderbilt University Medical Center, where she leads the PGY2 Oncology Residency Program and chairs the ASTCT Pharmacy SIG. Her expertise spans CAR T therapy, transplant conditioning, and GVHD therapies. Dr. Gatwood is an award-winning practitioner and has authored several publications on oncology pharmacy practice. Dr. Taha Al-Juhaishi is an attending physician and clinical investigator at OU Stephenson Cancer Center, Oklahoma's only NCI-designated center. He serves as associate director of the Hematopoietic Stem Cell Transplantation and Cell Therapy program and leads several clinical trials. Dr. Al-Juhaishi trained at Weill Cornell Medicine, VCU, and MD Anderson Cancer Center. Listeners will gain valuable insights into the complexities of managing outpatient CAR T therapy and strategies to enhance patient care.

Dr. Olga Klinkova covers essential information regarding the management of infectious complications of hematologic malignancies. Topics covered include the initial evaluation of patients, neutropenic fever, neutropenic enterocolitis, and antimicrobial prophylaxis. Next, Dr. Baluch discusses ID management of stem cell transplants, CAR-T therapy, and when it is necessary to administer antimicrobial prophylaxis in these patients. The lecture is updated as of 2024.

Krish Patel, MD, Swedish Cancer Institute, Seattle, WA Recorded on June 6, 2024 Krish Patel, MD Director, Lymphoma Program Director, Hematologic Malignancies and Cellular Therapy Swedish Cancer Institute Seattle, WA Join us as Dr. Krish Patel from Swedish Cancer Institute explores mantle cell lymphoma, including the goals and latest advancements in treatment. He also provides insights on treating relapsed/refractory cases, discusses effective strategies for managing side effects, and highlights the importance of communication between patients and healthcare professionals for optimal care. Tune in to stay up to date on mantle cell lymphoma today!

Learn about a study in NEJM which found no significant benefits from discontinuing beta-blocker therapy in MI patients, gut microbiota's potential influence on hematologic cancers and, data from ESC Congress 2024 suggesting that catching up on sleep during weekends may reduce heart disease risk by up to 20%.

Dr. Cutler received his MD from McGill University, Montreal, Canada. Hesubsequently received his MPH from the Harvard school of Public Health. He completed postgraduate training in Internal Medicine at Royal Victoria Hospital, Montreal, followed by a fellowship in Hematology/Oncology at DFCI. In 2002, he joined DFCI, where he currently is a member of the Hematologic Malignancies staff. Dr. Cutler is a Director of the Adult Cell Transplantation Program, Director of ClinicalResearch for Stem Cell Transplantation and Director of the Stem Cell TransplantationSurvivorship Program. He also works as an Associate Professor of Medicine at Harvard Medical School.

Dr. Doris Ponce from Memorial Sloan Kettering Cancer Center delves into atypical presentations of chronic graft-versus-host disease (cGVHD). As an associate member, co-chair of the Center for Hematologic Malignancies, and director of the Graft-Versus-Host Disease Program, Dr. Ponce provides an in-depth understanding of this complex condition.Dr. Ponce emphasizes the diverse symptoms of GVHD that often overlap with other conditions, making diagnosis challenging. She outlines the eight organs typically affected by GVHD: skin, mouth, eyes, musculoskeletal, genitourinary, lungs, liver, and gastrointestinal tract. However, she highlights that GVHD can also present atypically in organs such as the kidneys, nervous system, muscles, heart, and pancreas, causing symptoms such as serositis, effusions, nephrotic syndrome, and autoimmune disorders like vitiligo.Atypical presentations of GVHD are rare and require exclusion of other conditions such as drug side effects or infections before diagnosis. Dr. Ponce stresses the importance of patients communicating any new or unusual symptoms with their clinicians, as these might not initially seem connected to GVHD.Focusing on skin-related GVHD, Dr. Ponce describes common and atypical manifestations, including tight skin (sclerodermatous changes), pigmentation loss, dryness, and psoriasis-like appearances. Treatment varies but often involves topical steroids or immune suppression tailored to individual symptoms. For daily skincare, she advises avoiding frequent hot showers, using lukewarm water, and selecting gentle, fragrance-free products to prevent skin irritation.Regarding sun exposure, Dr. Ponce recommends using broad-spectrum sunscreen with SPF 30 or higher, and wearing protective clothing to prevent rashes exacerbated by sunlight. She also discusses the use of chemical and mineral sunscreens, noting that mineral sunscreens, despite being thicker, are better suited for sensitive skin.Peggy and Dr. Ponce discuss the Long Good Feel Better program that the American Cancer Society provides. For patients wanting to wear makeup, Dr. Ponce suggests choosing products designed for sensitive skin, avoiding those with harsh ingredients or multiple components, and replacing makeup regularly to prevent contamination. She also warns against using organic or preservative-free makeup due to infection risks.Haircare after GVHD often involves managing hair loss and changes in texture. Dr. Ponce advises infrequent washing, using gentle products, and considering supplements like biotin. For wigs, she cautions against those requiring glue and suggests alternatives like clip-on wigs or scarves. Hair dyeing is permissible with ammonia-free products.Nail care post-transplant includes using nail hardeners and avoiding acrylic nails. Dr. Ponce also emphasizes checking for underlying issues like vitamin deficiencies that may affect nail health.In closing, Dr. Ponce highlights the holistic approach to patient care at Memorial Sloan Kettering Cancer Center, addressing both medical and psychological aspects to support patients' overall well-being. She encourages patients to communicate any concerns, as seemingly minor symptoms might significantly impact their health and recovery. Dr. Ponce's dedication to improving patients' lives extends beyond treating their conditions, fostering confidence and quality of life throughout their recovery journey.More:Memorial Sloan Kettering Cancer Center's Tips for Managing GVHD (created by Dr. Ponce and dermatologist) Dr. Alina Markova:https://www.mskcc.org/cancer-care/patient-education/tips-managing-graft-versus-host-disease-gvhdAmerican Cancer Society's Look Good Feel Better Program: https://lookgoodfeelbetter.org/Memorial Sloan Kettering Cancer Center Website: https://www.mskcc.org/Sally Hansen Nail Hardener: https://www.sallyhansen.com/en-us/nail-care/nail-care/mega-strength-hardenerSurvivor recommended clothing brands that have SPF/UPF clothing:Coolibar: https://www.coolibar.com/Columbia: https://www.columbia.com/c/sun-protection/Baleaf: https://www.baleaf.com/collections/upf50This season is made possible thanks to donations from Syndax and Incyte.https://syndax.com/https://incyte.com/ Follow the nbmtLINK on Instagram! https://www.instagram.com/nbmtlink/

In a conversation with CancerNetwork®, Nausheen Ahmed, MD, spoke about optimizing monitoring strategies for patients with B-cell non-Hodgkin lymphoma who undergo treatment with CAR T-cell therapy. Ahmed, an associate professor in the Division of Hematologic Malignancies and Cellular Therapeutics at the University of Kansas Medical Center, discussed the possibility of offering more flexible monitoring periods for patients in the context of findings from a real-world study published in Blood Advances.1 Data from her study showed that the occurrence of new onset cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) was rare at more than 2 weeks following CAR T-cell therapy infusion. Additionally, late non-relapse mortality generally resulted from infectious complications. The FDA implemented a Risk Evaluation and Mitigation Strategy (REMS) to help manage the risk of severe CRS and ICANS by requiring patients to reside within 2 hours of an authorized treatment center for 4 weeks following CAR T-cell therapy infusion.2 According to the study authors, this mitigation strategy may create significant barriers to CAR T-cell therapy access among certain patients and caregivers who need to relocate as part of a treatment plan.  Findings from Ahmed's study supported the development of individualized monitoring strategies depending on the stability of the patient. She and her coauthors proposed a 2-week monitoring period for patients while allowing for an optional increase to 4 weeks based on factors such as physician comfort and availability of local community oncology support. As Ahmed emphasized during the discussion, having flexibility in these monitoring periods could help mitigate financial and geographic obstacles preventing adequate access to CAR T-cell therapy among patients. “There has to be more of a hybrid model of care. There has to be more involvement of our referring doctors or community doctors in detecting and managing these infections or working with the specialized center in order to bypass the [emergency room] and other strategies to help these patients,” Ahmed said. “If there is enough data to say that the patients do not need extra restrictions beyond 2 weeks, which is what our studies show, then reconsidering the requirements will be one step towards decreasing disparities in access.” References 1.        Ahmed N, Wesson W, Lutfi F, et al. Optimizing the post-CAR T monitoring period in recipients of axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. Blood Advances. Published online July 24, 2024. doi:10.1182/bloodadvances.2023012549 2.        Risk Evaluation and Mitigation Strategies (REMS) for autologous chimeric antigen receptor (CAR) T cell immunotherapies modified to minimize burden on healthcare delivery system. FDA. June 26, 2024. Accessed July 23, 2024. https://tinyurl.com/2m284rjy

Introduced by Associate Editor Robert Zeiser, this Review Series focuses on the problem of immune escape by acute myeloid leukemia (AML). The series opens with a review of how AML escapes T-cell–driven elimination and then focuses on how p53 function impinges on AML recognition by immune cells. The series finishes with a summary of new approaches to tackling this major problem.Featured Series:Introduction to a review series on oncogenic signaling and immune evasion in hematologic malignancies

At the 2024 European Hematology Association (EHA) Congress, CancerNetwork® spoke with a variety of experts in the hematologic oncology space about optimizing outcomes across different patient populations and subgroups based on updated research they presented at the meeting.  Manali Kamdar, MD, an associate professor of medicine-hematology and clinical director of Lymphoma Services at the University of Colorado Anschutz Medical Campus, in Colorado, spoke about data from the phase 1 TRANSCEND NHL 001 trial (NCT02631044) supporting the use of lisocabtagene maraleucel (liso-cel; Breyanzi) in earlier lines of therapy for patients with relapsed/refractory mantle cell lymphoma (MCL).1  Specifically, Kamdar highlighted how research should continue to focus on the potential utility of liso-cel in MCL subgroups such as those with TP53 mutations or blastoid morphology. Additionally, she stated that liso-cel may need to be further tested in earlier lines of therapy for patients with diffuse large B-cell lymphoma, including those with double-hit lymphoma. Michael R. Grunwald, MD, chief of the Leukemia Division and director of the Transplantation and Cellular Therapy Program at Atrium Health's Levine Cancer Institute, in North Carolina, discussed findings from the Prospective Observational Study of Patients With Polycythemia Vera (PV) in US Clinical Practices Trial (REVEAL) exploring risk factors for disease progression in patients with polycythemia vera (PV).2 According to Grunwald, a history of thromboembolic events, elevated white blood cell counts, and higher variant allele frequencies may contribute to a patient's likelihood of experiencing progression to myelofibrosis or acute myeloid leukemia (AML). Additionally, he highlighted ongoing research into the potential molecular factors that may prognosticate disease transformation in PV among a small cohort of patients enrolled on the REVEAL trial.3 Harry P. Erba, MD, PhD, a professor of medicine in the Division of Hematologic Malignancies and Cellular Therapy and the director of the Leukemia Program and Phase I Development in Hematologic Malignancies at Duke Cancer Institute, in North Carolina, discussed the clinical implications of data from the phase 3 QuANTUM-First study (NCT02668653).4  Specifically, findings demonstrated that continuation therapy with quizartinib (Vanflyta) elicited a more pronounced survival benefit vs placebo in patients with newly diagnosed FLT3-ITD–positive AML who did not undergo allogeneic hematopoietic stem cell transplant (allo-HSCT). However, Erba noted that survival outcomes were not significantly different in the quizartinib and placebo arms among patients who received allo-HSCT. References 1.        Palomba ML, Siddiqi T, Gordon LI, et al. Subgroup analyses in patients with R/R MCL treated with lisocabtagene maraleucel by prior lines of therapy and response to Bruton tyrosine kinase inhibitor from the TRANSCEND NHL 001 MCL cohort. Presented at the European Hematology Association (EHA) 2024 Congress; Madrid, Spain; June 13-16, 2024. P1126. 2.        Grunwald M, Zwicker J, Gerds A, et al. A real-world evaluation of risk factors for disease progression in patients with polycythemia vera (PV) enrolled in REVEAL. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract P1047. 3.        Crowgey E, Timmers C, Xue Z, et al. Analysis of molecular mechanisms and predictive biomarkers of disease transformation in polycythemia vera. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract S217. 4.        Sekeres MA, Erba H, Montesinos P, et al. QuANTUM-First: efficacy in newly diagnosed patients with FMS-like tyrosine kinase 3-internal tandem duplication–positive (FLT3-ITD+) acute myeloid leukemia (AML) who received continuation therapy. Presented at the 2024 European Hematology Association (EHA) Congress; June 13-16, 2024; Madrid, Spain. Abstract S142.

Understanding Cardiovascular Risks of BTK Inhibitors in Hematologic Malignancies: Muhammad Salman Faisal, MBBS by i3 Health

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

In this episode, Danielle M. Brander, MD; Deborah Stephens, DO; and Brian Hill, MD, PhD, discuss key aspects of the NCCN CLL guidelines and share strategies for applying these recommendations in your clinical practice to optimize treatment and outcomes. The greater discussion addresses:Optimal selection of therapy for treatment-naive CLL, including second-generation covalent BTK inhibitorsConsiderations in therapy selection for previously treated CLLNovel strategies for treating CLL Presenters:Danielle M. Brander, MDAssistant Professor of MedicineDivision of Hematologic Malignancies and Cellular TherapyDuke Cancer InstituteDurham, North CarolinaBrian Hill, MD, PhDDirector, Lymphoid Malignancies ProgramStaff Physician, Department of Hematology and Medical OncologyTaussig Cancer InstituteCleveland ClinicCleveland, OhioDeborah Stephens, DOAssociate ProfessorDirector of the CLL ProgramLineberger Comprehensive Cancer CenterUniversity of North CarolinaChapel Hill, North CarolinaContent based on a live and online CME program supported by educational grants from AstraZeneca; BeiGene, Ltd.; and Lilly.Link to full program including downloadable slides: https://bit.ly/49YxtSq

In this episode, we talk about GVHD prophylaxis, including recent data on post-transplant cyclophosphamide and abatacept with Dr. Shernan Holtan from the University of Minnesota. Here are the key trials we discussed:1. BMT CTN 1203 trial: Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of GVHD in allogeneic transplantation. https://pubmed.ncbi.nlm.nih.gov/30824040/ 2. BMT CTN 1703 study: Post-Transplantation Cyclophosphamide-Based GVHD prophylaxis  https://pubmed.ncbi.nlm.nih.gov/37342922/ 3. Patient-Reported Outcomes of BMT CTN 1703 https://ash.confex.com/ash/2023/webprogram/Paper187859.html 4. Phase II Study of Myeloablative 7-8/8-Matched Allotransplantation with Post-Transplantation Cyclophosphamide, Tacrolimus, and Mycophenolate Mofetil https://pubmed.ncbi.nlm.nih.gov/37311510/ 5. BMT CTN 1301 trial: Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies https://pubmed.ncbi.nlm.nih.gov/34855460/ 6. Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD (ABA2) https://pubmed.ncbi.nlm.nih.gov/33449816/ 7. Aurora Kinase a Inhibition for Gvhd and Relapse Prevention after Allogeneic HCT: Phase I Trial in Combination with Ptcy/Sirolimus https://ash.confex.com/ash/2023/webprogram/Paper181292.html

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/JXH865. CME credit will be available until December 31, 2024.Toward a Brighter Future for Preventing COVID-19 in Patients With Hematologic Malignancies: Leveraging the Power of Current Strategies and Next-Generation AgentsPenn State College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education.SupportThis activity is supported by an independent educational grant from AstraZeneca LP.DisclosuresShmuel Shoham, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Adagio Therapeutics, Inc.; Adamis Pharmaceuticals Corporation; Immunome; Karius, Inc.; Pfizer; and SCYNEXIS, Inc.Grant/Research Support from Ansun Biopharma; Cidara Therapeutics, Inc.; F2G; Octapharma USA, Inc.; and Zeteo Biomedical LLC.Ghady Haidar, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca and Karius, Inc.Grant/Research Support from Allovir; AstraZeneca; Karius, Inc.; and National Institutes of Health (NIH).Speaker for International AIDS Society and MDOutlook.Carol Ann Huff, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Janssen Pharmaceuticals, Inc. and Sanofi.Haleh Simi has no financial interests/relationships or affiliations in relation to this activity.Other PVI staff who may potentially review content for this activity have disclosed no relevant financial relationships.Penn State College of Medicine staff and faculty involved in the development and review of this activity have disclosed no relevant financial relationships.All of the relevant financial relationships listed for these individuals have been mitigated.

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/JXH865. CME credit will be available until December 31, 2024.Toward a Brighter Future for Preventing COVID-19 in Patients With Hematologic Malignancies: Leveraging the Power of Current Strategies and Next-Generation AgentsPenn State College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education.SupportThis activity is supported by an independent educational grant from AstraZeneca LP.DisclosuresShmuel Shoham, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Adagio Therapeutics, Inc.; Adamis Pharmaceuticals Corporation; Immunome; Karius, Inc.; Pfizer; and SCYNEXIS, Inc.Grant/Research Support from Ansun Biopharma; Cidara Therapeutics, Inc.; F2G; Octapharma USA, Inc.; and Zeteo Biomedical LLC.Ghady Haidar, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca and Karius, Inc.Grant/Research Support from Allovir; AstraZeneca; Karius, Inc.; and National Institutes of Health (NIH).Speaker for International AIDS Society and MDOutlook.Carol Ann Huff, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Janssen Pharmaceuticals, Inc. and Sanofi.Haleh Simi has no financial interests/relationships or affiliations in relation to this activity.Other PVI staff who may potentially review content for this activity have disclosed no relevant financial relationships.Penn State College of Medicine staff and faculty involved in the development and review of this activity have disclosed no relevant financial relationships.All of the relevant financial relationships listed for these individuals have been mitigated.

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/JXH865. CME credit will be available until December 31, 2024.Toward a Brighter Future for Preventing COVID-19 in Patients With Hematologic Malignancies: Leveraging the Power of Current Strategies and Next-Generation AgentsPenn State College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education.SupportThis activity is supported by an independent educational grant from AstraZeneca LP.DisclosuresShmuel Shoham, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Adagio Therapeutics, Inc.; Adamis Pharmaceuticals Corporation; Immunome; Karius, Inc.; Pfizer; and SCYNEXIS, Inc.Grant/Research Support from Ansun Biopharma; Cidara Therapeutics, Inc.; F2G; Octapharma USA, Inc.; and Zeteo Biomedical LLC.Ghady Haidar, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca and Karius, Inc.Grant/Research Support from Allovir; AstraZeneca; Karius, Inc.; and National Institutes of Health (NIH).Speaker for International AIDS Society and MDOutlook.Carol Ann Huff, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Janssen Pharmaceuticals, Inc. and Sanofi.Haleh Simi has no financial interests/relationships or affiliations in relation to this activity.Other PVI staff who may potentially review content for this activity have disclosed no relevant financial relationships.Penn State College of Medicine staff and faculty involved in the development and review of this activity have disclosed no relevant financial relationships.All of the relevant financial relationships listed for these individuals have been mitigated.

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/JXH865. CME credit will be available until December 31, 2024.Toward a Brighter Future for Preventing COVID-19 in Patients With Hematologic Malignancies: Leveraging the Power of Current Strategies and Next-Generation AgentsPenn State College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education.SupportThis activity is supported by an independent educational grant from AstraZeneca LP.DisclosuresShmuel Shoham, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Adagio Therapeutics, Inc.; Adamis Pharmaceuticals Corporation; Immunome; Karius, Inc.; Pfizer; and SCYNEXIS, Inc.Grant/Research Support from Ansun Biopharma; Cidara Therapeutics, Inc.; F2G; Octapharma USA, Inc.; and Zeteo Biomedical LLC.Ghady Haidar, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca and Karius, Inc.Grant/Research Support from Allovir; AstraZeneca; Karius, Inc.; and National Institutes of Health (NIH).Speaker for International AIDS Society and MDOutlook.Carol Ann Huff, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Janssen Pharmaceuticals, Inc. and Sanofi.Haleh Simi has no financial interests/relationships or affiliations in relation to this activity.Other PVI staff who may potentially review content for this activity have disclosed no relevant financial relationships.Penn State College of Medicine staff and faculty involved in the development and review of this activity have disclosed no relevant financial relationships.All of the relevant financial relationships listed for these individuals have been mitigated.

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/JXH865. CME credit will be available until December 31, 2024.Toward a Brighter Future for Preventing COVID-19 in Patients With Hematologic Malignancies: Leveraging the Power of Current Strategies and Next-Generation AgentsPenn State College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education.SupportThis activity is supported by an independent educational grant from AstraZeneca LP.DisclosuresShmuel Shoham, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Adagio Therapeutics, Inc.; Adamis Pharmaceuticals Corporation; Immunome; Karius, Inc.; Pfizer; and SCYNEXIS, Inc.Grant/Research Support from Ansun Biopharma; Cidara Therapeutics, Inc.; F2G; Octapharma USA, Inc.; and Zeteo Biomedical LLC.Ghady Haidar, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca and Karius, Inc.Grant/Research Support from Allovir; AstraZeneca; Karius, Inc.; and National Institutes of Health (NIH).Speaker for International AIDS Society and MDOutlook.Carol Ann Huff, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Janssen Pharmaceuticals, Inc. and Sanofi.Haleh Simi has no financial interests/relationships or affiliations in relation to this activity.Other PVI staff who may potentially review content for this activity have disclosed no relevant financial relationships.Penn State College of Medicine staff and faculty involved in the development and review of this activity have disclosed no relevant financial relationships.All of the relevant financial relationships listed for these individuals have been mitigated.

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/JXH865. CME credit will be available until December 31, 2024.Toward a Brighter Future for Preventing COVID-19 in Patients With Hematologic Malignancies: Leveraging the Power of Current Strategies and Next-Generation AgentsPenn State College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education.SupportThis activity is supported by an independent educational grant from AstraZeneca LP.DisclosuresShmuel Shoham, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Adagio Therapeutics, Inc.; Adamis Pharmaceuticals Corporation; Immunome; Karius, Inc.; Pfizer; and SCYNEXIS, Inc.Grant/Research Support from Ansun Biopharma; Cidara Therapeutics, Inc.; F2G; Octapharma USA, Inc.; and Zeteo Biomedical LLC.Ghady Haidar, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca and Karius, Inc.Grant/Research Support from Allovir; AstraZeneca; Karius, Inc.; and National Institutes of Health (NIH).Speaker for International AIDS Society and MDOutlook.Carol Ann Huff, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Janssen Pharmaceuticals, Inc. and Sanofi.Haleh Simi has no financial interests/relationships or affiliations in relation to this activity.Other PVI staff who may potentially review content for this activity have disclosed no relevant financial relationships.Penn State College of Medicine staff and faculty involved in the development and review of this activity have disclosed no relevant financial relationships.All of the relevant financial relationships listed for these individuals have been mitigated.

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/JXH865. CME credit will be available until December 31, 2024.Toward a Brighter Future for Preventing COVID-19 in Patients With Hematologic Malignancies: Leveraging the Power of Current Strategies and Next-Generation AgentsPenn State College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education.SupportThis activity is supported by an independent educational grant from AstraZeneca LP.DisclosuresShmuel Shoham, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Adagio Therapeutics, Inc.; Adamis Pharmaceuticals Corporation; Immunome; Karius, Inc.; Pfizer; and SCYNEXIS, Inc.Grant/Research Support from Ansun Biopharma; Cidara Therapeutics, Inc.; F2G; Octapharma USA, Inc.; and Zeteo Biomedical LLC.Ghady Haidar, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca and Karius, Inc.Grant/Research Support from Allovir; AstraZeneca; Karius, Inc.; and National Institutes of Health (NIH).Speaker for International AIDS Society and MDOutlook.Carol Ann Huff, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Janssen Pharmaceuticals, Inc. and Sanofi.Haleh Simi has no financial interests/relationships or affiliations in relation to this activity.Other PVI staff who may potentially review content for this activity have disclosed no relevant financial relationships.Penn State College of Medicine staff and faculty involved in the development and review of this activity have disclosed no relevant financial relationships.All of the relevant financial relationships listed for these individuals have been mitigated.

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/JXH865. CME credit will be available until December 31, 2024.Toward a Brighter Future for Preventing COVID-19 in Patients With Hematologic Malignancies: Leveraging the Power of Current Strategies and Next-Generation AgentsPenn State College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education.SupportThis activity is supported by an independent educational grant from AstraZeneca LP.DisclosuresShmuel Shoham, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Adagio Therapeutics, Inc.; Adamis Pharmaceuticals Corporation; Immunome; Karius, Inc.; Pfizer; and SCYNEXIS, Inc.Grant/Research Support from Ansun Biopharma; Cidara Therapeutics, Inc.; F2G; Octapharma USA, Inc.; and Zeteo Biomedical LLC.Ghady Haidar, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca and Karius, Inc.Grant/Research Support from Allovir; AstraZeneca; Karius, Inc.; and National Institutes of Health (NIH).Speaker for International AIDS Society and MDOutlook.Carol Ann Huff, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Janssen Pharmaceuticals, Inc. and Sanofi.Haleh Simi has no financial interests/relationships or affiliations in relation to this activity.Other PVI staff who may potentially review content for this activity have disclosed no relevant financial relationships.Penn State College of Medicine staff and faculty involved in the development and review of this activity have disclosed no relevant financial relationships.All of the relevant financial relationships listed for these individuals have been mitigated.

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/JXH865. CME credit will be available until December 31, 2024.Toward a Brighter Future for Preventing COVID-19 in Patients With Hematologic Malignancies: Leveraging the Power of Current Strategies and Next-Generation AgentsPenn State College of Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.This activity is developed in collaboration with our educational partner, PVI, PeerView Institute for Medical Education.SupportThis activity is supported by an independent educational grant from AstraZeneca LP.DisclosuresShmuel Shoham, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Adagio Therapeutics, Inc.; Adamis Pharmaceuticals Corporation; Immunome; Karius, Inc.; Pfizer; and SCYNEXIS, Inc.Grant/Research Support from Ansun Biopharma; Cidara Therapeutics, Inc.; F2G; Octapharma USA, Inc.; and Zeteo Biomedical LLC.Ghady Haidar, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for AstraZeneca and Karius, Inc.Grant/Research Support from Allovir; AstraZeneca; Karius, Inc.; and National Institutes of Health (NIH).Speaker for International AIDS Society and MDOutlook.Carol Ann Huff, MD, has a financial interest/relationship or affiliation in the form of:Consultant and/or Advisor for Janssen Pharmaceuticals, Inc. and Sanofi.Haleh Simi has no financial interests/relationships or affiliations in relation to this activity.Other PVI staff who may potentially review content for this activity have disclosed no relevant financial relationships.Penn State College of Medicine staff and faculty involved in the development and review of this activity have disclosed no relevant financial relationships.All of the relevant financial relationships listed for these individuals have been mitigated.

BUFFALO, NY- December 27, 2023 – A new #research paper was #published in Oncotarget's Volume 14 on December 20, 2023, entitled, “The pharmacodynamic and mechanistic foundation for the antineoplastic effects of GFH009, a potent and highly selective CDK9 inhibitor for the treatment of hematologic malignancies.” To evade cell cycle controls, malignant cells rely upon rapid expression of select proteins to mitigate pro-apoptotic signals resulting from damage caused by both cancer treatments and unchecked over-proliferation. Cyclin-dependent kinase 9 (CDK9)-dependent signaling induces transcription of downstream oncogenes promoting tumor growth, especially in hyperproliferative ‘oncogene-addicted' cancers, such as human hematological malignancies (HHMs). In this new study, researchers Fusheng Zhou, Lili Tang, Siyuan Le, Mei Ge, Dragan Cicic, Fubo Xie, Jinmin Ren, Jiong Lan, and Qiang Lu from GenFleet Therapeutics Inc. and Sellas Life Sciences Group aimed to summarize current knowledge underlying the mechanism of action (MOA) of GFH009 and explain its robust anti-cancer activity. “Understanding GFH009's MOA allows for a more optimal clinical development path, given the potential for meaningful benefits in patients with hematological malignancies.” GFH009, a potent, highly selective CDK9 small molecule inhibitor, demonstrated antiproliferative activity in assorted HHM-derived cell lines, inducing apoptosis at IC50 values below 0.2 μM in 7/10 lines tested. GFH009 inhibited tumor growth at all doses compared to controls and induced apoptosis in a dose-dependent manner. Twice-weekly injections of GFH009 maleate at 10 mg/kg significantly prolonged the survival of MV-4-11 xenograft-bearing rodents, while their body weight remained stable. There was marked reduction of MCL-1 and c-MYC protein expression post-drug exposure both in vitro and in vivo. Through rapid ‘on-off' CDK9 inhibition, GFH009 exerts a proapoptotic effect on HHM preclinical models triggered by dynamic deprivation of crucial cell survival signals. “Our results mechanistically establish CDK9 as a targetable vulnerability in assorted HHMs and, along with the previously shown superior class kinome selectivity of GFH009 vs other CDK9 inhibitors, strongly support the rationale for currently ongoing clinical studies with this agent in acute myeloid leukemia and other HHMs.” DOI - https://doi.org/10.18632/oncotarget.28543 Correspondence to - Jiong Lan - jlan@genfleet.com Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28543 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, GFH009, CDK9, leukemia, cell cycle 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: SoundCloud - https://soundcloud.com/oncotarget 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/ Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

We talked with the Chief of the Division of Hematologic Malignancies and Co-Director of the Adult Stem Cell Transplantation Program at Dana Farber Cancer Institute about the process of being a donor and the impact you have on others lives.

Robert Soiffer, MD, is the Chief of the Division of Hematologic Malignancies at Dana Farber Cancer Institute and the Worthington and Margaret Collette Professor of Medicine at Harvard Medical School. A renowned malignant hematology researcher, Dr. Soiffer has served as President of the American Society of Blood and Marrow Transplantation and is the immediate past chair of the board of the National Marrow Donor Program. He has co-authored more than 400 peer-reviewed manuscripts, book chapters, review articles, editorials, and monographs. “Early in my career, when I would mentor people, I would explain to them exactly how I did what I did. A lot of folks would say, I want to be like you. But you need to realize that you're not like me, you're different, you're YOU. So you have to find your own path.” Known as a “mentor to mentors”, Dr. Robert Soiffer teaches us how to best utilize mentors to carve our own path, how JOY in medicine lies in the JOurneY not necessarily the outcomes, and the ephemeral nature of success, which is why “you can't enjoy the successes too much or wallow in the failures too much because they're going to flip around.” Pearls of Wisdom:   1. We have to remember history in order to define the present and improve the future. The greatest memory tool is talking to the patient, asking the patient, and letting that serve as the way we remember their story. 2. Don't connect failure or success to the end result; focus on improving the journey and finding joy in that process. 3. You don't have to be a mentor's shadow; talk about your path and vision with them to gain insight on how you can achieve that. 4. Have fun everyday and never miss a meal.

  “I think the take-home message here, though, is to have very specific guidelines at your institution to manage both CRS and ICANS. The protocols should be readily available to all practitioners who may participate in the care of these patients,” ONS member Phyllis McKiernan, MSN, APN, OCN®, advanced practice provider at the John Theurer Cancer Center at Hackensack University Medical Center in New Jersey, told Lenise Taylor, MN, RN, AOCNS®, BMTCN®, oncology clinical specialist at ONS. McKiernan's and Taylor's conversation centered around the nurse's role in recognizing and managing toxicities related to CAR T-cell therapy for hematologic malignancies, specifically ICANS and CRS, which was an educational priority that ONS members identified during two ONS focus groups on the topic in March 2023. McKiernan was one of the content experts for those focus groups.  This podcast episode is produced by ONS and supported by funding from Janssen Oncology/Legend Biotech. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications.   Music Credit: “Fireflies and Stardust” by Kevin MacLeod   Licensed under Creative Commons by Attribution 3.0    Episode Notes  NCPD contact hours are not available for this episode.  Oncology Nursing Podcast episodes: Oncologic Emergencies 101 series Episode 261: CAR T-Cell Therapy for Hematologic Malignancies Requires Education and Navigation Episode 139: How CAR and Other T Cells Are Revolutionizing Cancer Treatment Episode 1: Experiences With CAR T-Cell Therapy ONS Clinical Practice Resources: Chimeric Antigen Receptor T-Cell Therapy: A Timeline of Events and Adverse Events Cytokine Release Syndrome ONS Clinical Update: Focus on Clinical Experiences With CAR T-Cell Therapy ONS course: Nursing Considerations for CAR T-Cell Therapy for Patients With Hematologic Malignancies: Patient Education and Symptom Management ONS Huddle Card™️: Cytokine Release Syndrome ONS Immuno-Oncology Learning Library ONS videos: CAR T-Cell Therapy Cytokine Release Syndrome American Cancer Society American Society for Transplantation and Cellular Therapy Grading Scale for CRS and ICANS Leukemia and Lymphoma Society  Multiple Myeloma Research Foundation  National Institutes of Health's National Cancer Institute Risk Evaluation and Mitigation Strategies   To discuss the information in this episode with other oncology nurses, visit the ONS Communities.   To find resources for creating an ONS Podcast Club in your chapter or nursing community, visit the ONS Podcast Library.   To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org.   Highlights From Today's Episode  “All symptoms need to be investigated fully to determine their cause and thus the best management strategy and not just simply assume that they're related to CAR T.” Timestamp (TS) 9:21   “Accurate grading is really crucial to ensure that the toxicities are identified and managed consistently across the institution.” TS 10:52  “Once the patient shows signs and symptoms of neurotoxicity, they should have a comprehensive neurologic examine, and that should include, a neurology consult, maybe imaging, such as an MRI or CT, and perhaps even a lumbar puncture.” TS 14:12  “Letting patients and their families know what next steps are can alleviate anxiety and give the patients the confidence that the medical team is familiar with these toxicities. And let them know that these toxicities are expected and that there are protocols in place to manage these symptoms.” TS 22:56  “I think that some patients, and even healthcare professionals, who aren't familiar with CAR T believe that the toxicities are always severe and always irreversible. When, in reality, most of the toxicities are mild and managed with minimal intervention or even just supportive care.” TS 23:55   “Early detection, consistent grading, vigilant monitoring, and standardized care plans are crucial to the success of any CAR T program and can also help reduce the risk of the severe adverse effects and hopefully improve outcomes for our patients.” TS 30:26 

Drs. John Sweetenham and Marc Braunstein discuss advances in hematologic malignancies featured at the 2023 ASCO Annual Meeting, including the potentially practice-changing SWOG-S1826 study in Hodgkin lymphoma, the promise of bispecific antibodies in B-cell malignancies, and a novel approach to deliver vital anti-myeloma medications that could improve patient quality of life and alleviate barriers to care. TRANSCRIPT   Dr. John Sweetenham: Hello, I'm John Sweetenham, the associate director for cancer network clinical affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and the host of the ASCO Daily News Podcast.    The 2023 ASCO Annual Meeting featured some exciting new data on hematologic malignancies. I'm delighted to have Dr. Marc Braunstein return to the podcast to discuss some of these potentially practice-changing studies and new approaches in the heme space. Dr. Braunstein is a hematologist and oncologist at the NYU Perlmutter Cancer Center.    You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the ASCO Daily News Podcast are available on our transcripts at asco.org/DNpod.   Marc, it's great to have you back on the podcast, and thanks for being here again.   Dr. Marc Braunstein: Thank you, John. It's great to be back.   Dr. John Sweetenham: Marc, we already mentioned that there are some potentially practice-changing studies that were reported at ASCO this year. And among those, LBA4, which was presented in the Plenary Session, was a study which explored the treatment of advanced Hodgkin lymphoma. This was the Southwest Oncology Group study S1826. Could you give us your insights on this?    Dr. Marc Braunstein: Sure, happy to discuss S1826. So as background, you know, the ECHELON-1 study, which was published in the New England Journal of Medicine in 2022 showed a 40% decrease in the risk of death at six years follow-up by adding brentuximab to AVD compared to bleomycin AVD. And that was in high risk or advanced-stage patients and that led to adoption of brentuximab for upfront use in patients with classical Hodgkin lymphoma in advanced stage.    Also of note, immune checkpoint inhibitors such as pembrolizumab or nivolumab do have activity in the relapse setting. The SWOG S1826 study was a randomized control study looking at the use of the PD-1 inhibitor nivolumab plus AVD versus brentuximab AVD in patients with advanced stage classical Hodgkin lymphoma who are at least twelve years of age. And the primary endpoint in the study was progression-free survival.     It was a large study which enrolled 976 patients and randomized them one to one to either nivo AVD or brentuximab AVD. The median age in the study was 27 and the median follow-up was 12 months. And what the study found, which could be practice-changing, was that the primary endpoint of progression-free survival was superior in the nivolumab arm with a hazard ratio of 0.8 and a one-year PFS of 94% versus 86%, favoring the nivolumab arm. And while there were side effects associated with the class of medications, for example, hypo or hyperthyroidism was more frequent in the nivolumab group, whereas peripheral neuropathy was higher in the brentuximab group, I think that these results are particularly encouraging for how we can continue to improve outcomes for patients with advanced-stage classical Hodgkin lymphoma. And this may be practice-changing in terms of whether we use upfront immune checkpoint inhibitors in combination with our standard chemotherapy backbone.    Dr. John Sweetenham: Yeah, absolutely. There are a couple of things that occur to me. One in particular which is unique about this study, and the fact that it was for patients who are 12 years and older in many respects represents a first because I can't think of another large, randomized study of this type which has attempted to align pediatric and adult care of patients with Hodgkin lymphoma. So, I think it's something of a landmark in that regard. I don't know if you'd agree with that.    Dr. Marc Braunstein: I agree, especially with the range of ages from 12 to 83. It's a pretty broad population by age, but I agree it does kind of reconcile those two groups in a disease that has a bimodal presentation and clearly shows that immune checkpoint inhibitors are both potent and well tolerated in different age groups.    Dr. John Sweetenham: The other question that I have about this study is we haven't seen so far in this study an overall survival benefit to the nivo arm, which is maybe not surprising, but in terms of the practice-changing potential of this study, do you think that will matter?   Dr. Marc Braunstein:  I think that's an excellent question, John. Initially, the ECHELON-1 study only showed progression-free survival, and then the update did show overall survival. And so if we take the lead from that study, we expect to see an overall survival benefit in the SWOG study as well with nivolumab, but it remains to be seen. But I think that the data presented thus far at the Plenary Session is compelling enough to consider using nivolumab upfront.   Dr. John Sweetenham: Yeah, I absolutely agree. And then I guess the other question that we're going to have to wait probably several years to know is what happens in terms of relapse? So, for the minority of these patients who do relapse, how salvageable, if that's the right word, are they going to be with a second- or third-line regimen? But I think that's clearly something for the future, and it's a very interesting, exciting outcome from this study.   Dr. Marc Braunstein: Absolutely.    Dr. John Sweetenham: Let's move on. Marc, again, we're still in the lymphoma world here, but looking at high-risk follicular lymphoma. And this was Abstract 7506, looking at epcoritamab plus the R2 regimen in patients with follicular lymphoma. Could you walk us through this one?    Dr. Marc Braunstein: Yeah, absolutely. Bispecific T-cell engaging antibodies are showing impressive efficacy in relapsed and refractory non-Hodgkin lymphoma. Epcoritamab is a bispecific antibody that binds to CD3 on T-cells and CD20 B-cells. And this antibody is currently approved for diffuse large B-cell lymphoma patients after two or more prior lines of treatment.    In this study presented by Merryman and colleagues, they explored the addition of epcoritamab to standard lenalidomide-rituximab. In 109 patients with relapsed or refractory follicular lymphoma who had at least one prior therapy, and, of note, the study was enriched for high-risk patients for progression, including those who had progression of disease within 24 months of their initial treatment and those patients who had been refractory to prior anti-CD20 treatment. This study enrolled 109 patients with relapsed refractory follicular lymphoma. The median age was 65 and 56% of patients had FLIPI scores on the higher end of the spectrum from three to five, and 61% had stage 4 disease. Also of note, 38% of patients had progression of disease within 24 months of their prior treatment. So at a median follow-up of 8.8 months, the overall response rate was impressive at 97%, and 82% of patients were still on treatment at that time.     Now, of course, with this mechanism of action of bispecific antibodies, there is a risk of both cytokine release syndrome and immune-related neurotoxicity. The rates of CRS were primarily low grade, there were only 2% grade 3, and of note, most occurred after the first dose. And in terms of ICANS or neurological toxicity, there were no grade 3 adverse events, and those occurred in only two patients. Finally, the estimated six months progression-free survival was 93%. So, if we cross-compare these results historically to the R-squared regimen, which was published to be about 80%, just cross comparing, so it's not exactly the same study, this clearly shows high activity on par or better with R-squared alone. Although this study was not a randomized study, I think the addition of epcoritamab certainly shows high overall response rates and we'll need randomized data to confirm the efficacy, but it's definitely encouraging in high-risk follicular lymphoma patients.   Dr. John Sweetenham: Thanks, Marc. I agree. I think these data are really enticing, in as much as the response rates are so high, but of course, it is follicular lymphoma, so we'll have to wait a while. But the thing that it does make me reflect on is that bispecific antibodies really are turning out to be remarkably effective in a range of B cell malignancies, so, it's very interesting to continue to watch this space.    I'm going to change gears now and talk about something completely different for a moment. And this was Abstract 1536. I think that many of us are in a position where we're now looking at how we deliver our clinical services, and particularly inpatient services, to patients with hematologic malignancy. And this study addressed that very specifically. Can I have your thoughts on that?   Dr. Marc Braunstein: Sure. In the context of how our therapies are improving, our approaches to how we manage patients clinically is changing too, in many ways for the better. So, various models exist for, you know, which practitioners manage oncology patients who happen to be admitted to the hospital. This abstract, which was performed by authors at a large medical center in New York, describes the use of a dedicated hematologic malignancy hospitalist for managing medicine-related issues. And the authors did comparisons of that service to a service primarily managed by oncologists. The authors compared things such as length of stay, whether the patients were discharged by noon, which is a hospital metric that's used for facilitating turnover of patients and space availability, as well as 30-day readmission rates among patients cared for by an oncology attending versus this heme malignancy hospitalist between July of 2021 and July 2022.    The outcomes showed that admissions to the heme malignancy hospitalists were, although less because that service was primarily for patients who required medicine-related issues as opposed to primarily oncologic issues, there were 95 admissions to that service versus 669 to the oncology service. There was a significantly shorter length of stay on the heme malignancies hospitalist service by about 2 to 5 days compared to the oncology hospitalist service. The rates of patients who were discharged by noon or the length of stay were similar between the two groups.    So, while this study is confounded by differences in acuity of disease between the services, using a dedicated heme malignancy hospitalist has many benefits, not just to offload the oncology-managed service, which may have a higher level of acuity, but also allow for a deviation of care for medicine-specific issues, to a hospitalist that's specifically trained in managing patients with hematologic malignancies and then dedicating the oncology specialty service to those who need acute oncologic care, such as those with leukemia or other high acuity diseases.    Dr. John Sweetenham: Thanks, Marc. I think it is really interesting to see some outcome data for this model of care. A number of centers I know are looking at an APP-led inpatient service for these types of patients, too, so it's going to be very interesting to see how further studies of these kinds of approaches continue to develop.    And on a related theme of changes in patterns of care, Abstract TPS1609 looked at home infusion and of course, this is something that really started to attract a lot more attention during the COVID-19 pandemic. But I wonder if you could walk us through some of the details of this poster.    Dr. Marc Braunstein: This study was presented as a poster proposing a prospective study looking at home infusion of the anti-CD38 monoclonal antibody daratumumab, which has a vital role in managing patients with newly diagnosed or relapsed multiple myeloma. And monoclonal antibodies have really revolutionized the care of patients with multiple myeloma, but often their infusion schedule is weekly or biweekly, and it does require relatively frequent visits to an infusion center.    So, this single-arm, open-label study is going to examine whether we can provide home administration of subcutaneous daratumumab and assess whether it improves quality of life and assess its safety. So, in this study, a visiting nurse will come and deliver the medication after patients take their pre-medications at home prior to the arrival of the infusion nurse. And then the investigators will provide quality of life questionnaires prior to and after the infusions and at the end of the study, and they'll be looking at any barriers to adherence, any barriers to the logistics of this home infusion arrangement.    And I think that this has a lot of potential not just to improve quality of life, but also to facilitate care to patients who may be frail, who may not have good caregiver support, who may have barriers in traveling to an infusion center or perhaps in places that are more resource-deprived and don't have local infusion centers. This could be a potential approach to delivering vital anti-myeloma medications at home, and I'm looking forward to seeing the results.    Dr. John Sweetenham: Yeah, I agree. I think a lot of us still have anxieties about the safety of this approach, but I think there are increasing data to suggest that home infusion is not only safe but also, as you mentioned, is a big enhancer of the quality of life of these patients. And so, very interesting to see how this plays out in prospective studies.    So, to close out, I wonder if you could walk us through Abstract 7072, a poster looking at the issue of clonal hematopoiesis.    Dr. Marc Braunstein: Clonal hematopoiesis, which is a phenomenon in which the blood cells acquire somatic mutation, is associated with both cardiovascular disease adverse outcomes as well as hematologic malignancy. It's been shown to be a precursor for diseases such as leukemia. So, this relatively small study from MD Anderson Cancer Center examined clonal hematopoiesis in 78 patients with malignancies, 70% of which had a history of cancer, and the authors described outcomes associated with clonal hematopoiesis.    So, again, 78 patients were examined, and 76% of them had a history of malignancy, and 73% had other comorbidities. And the authors demonstrated clonal hematopoiesis by the finding of specific mutations in the blood associated with clonal hematopoiesis. The authors essentially looked at outcomes such as mortality. They noted that only 20% of the patients developed a myeloid neoplasm, and that's relevant because, again, clonal hematopoiesis is a precursor for myeloid neoplasms. They also noted that most patients had died from a primary malignancy rather than a myeloid neoplasm, which is not too surprising considering that most patients with clonal hematopoiesis will not develop a hematologic malignancy, but it is a marker for the potential transformation.    And so, I think the authors conclude that clonal hematopoiesis is important for monitoring patients who are at risk for potential myeloid transformation and hematologic malignancy, but it's not necessarily the case that patients who have a background of malignancy will often develop a myeloid malignancy. I think there are many implications of clonal hematopoiesis for cancer in general in terms of the risk of secondary malignancies in those treated with adjuvant chemotherapy, in terms of how we monitor patients who actually more and more are going to have this detected as we use more next-generation sequencing and liquid biopsies.     So, I look forward to future studies that are exploring how to actually prospectively assess clonal hematopoiesis and use it for clinical stratification for things like adjuvant chemotherapy or monitoring for risks of hematologic malignancy.    Dr. John Sweetenham: Thanks, Marc. I agree. Very important for the future, especially as we gain more and more sequencing data.    So, Marc, in conclusion, I want to thank you very much for sharing your insights with us today on the ASCO Daily News Podcast. It's been great to talk with you again.    Dr. Marc Braunstein: My pleasure. Happy to be back, and I look forward to a future podcast session.  Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcripts of this episode. Finally, if you value the insights that you hear on 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 speakers:   Dr. John Sweetenham   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        

Navneet Majhail, MD, MS, the Physician in Chief at Sarah Cannon in Nashville, Tennessee, delves into the intricacies of chimeric antigen receptor (CAR) T-cell therapy, discussing the logistics and challenges involved with these therapies. Dr. Majhail explores strategies to improve access to CAR-T therapy and he discusses the role of CAR-T amidst the availability of bispecific antibodies as treatments for blood cancers.

In this episode we are joined by F. Marc Stewart, MD, Vice Chair, Department of Hematology & Hematopoietic Cell Transplantation, Jeffrey R. Schriber, MD, FRCP, Director of Hematologic Malignancies, City of Hope Atlanta, Chicago and Phoenix, and Syed A. Abutalib, MD, Co-director, Hematologic Malignancies and Stem Cell Transplant Program, City of Hope Chicago as they discuss City of Hope's BMT and CAR T cell therapy programs, being leaders in the space, and ensuring integration across their national clinical network. This episode is sponsored by City of Hope.

“Just like with anything we do in oncology, a lot of education is required. Nurses and coordinators are critical to start the education and provide effective resources that are reinforced throughout the treatment,” ONS member Beth Faiman, PhD, MSN, APN-BC, AOCN®, BMTCN®, FAAN, FAPO, advanced practice provider at Cleveland Clinic in Ohio, told Lenise Taylor, MN, RN, AOCNS®, BMTCN®, oncology clinical specialist at ONS, during a conversation about how to address knowledge gaps and barriers to practice regarding patients who are preparing for or who have received CAR T-cell therapy for hematologic malignancies. Faiman was one of the content experts for two ONS focus groups on the topic in March 2023. This podcast episode is produced by ONS and supported by funding from Janssen Oncology and Legend Biotech. ONS is solely responsible for the criteria, objectives, content, quality, and scientific integrity of its programs and publications. Music Credit: “Fireflies and Stardust” by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 Episode Notes NCPD contact hours are not available for this episode. Oncology Nursing Podcast episodes: Episode 1: Experiences With CAR T-Cell Therapy Episode 139: How CAR and Other T Cells Are Revolutionizing Cancer Treatment Episode 176: Oncologic Emergencies 101: Cytokine Release Syndrome ONS Voice articles: Studies Show Best Practices to Manage CAR T-Cell Therapies' irAEs and Improve Outcomes CAR T-Cell Therapy Programs: Essential Elements to Establish a Successful System A Body of Evidence Helps Nurses Manage CAR T-Cell Therapy Toxicities Clinical Journal of Oncology Nursing articles: CAR T-Cell Therapy: Updates in Nursing Management Building a Program: Implications for Infrastructure, Nursing Education, and Training for CAR T-Cell Therapy Management Across Settings: An Ambulatory and Community Perspective for Patients Undergoing CAR T-Cell Therapy in Multiple Care Settings ONS clinical practice resources: Chimeric Antigen Receptor T-Cell Therapy: A Timeline of Events and Adverse Events Cytokine Release Syndrome ONS course: Nursing Considerations for CAR T-Cell Therapy for Patients With Hematologic Malignancies: Patient Education and Symptom Management ONS videos: CAR T-Cell Therapy Cytokine Release Syndrome American Society for Transplantation and Cellular Therapy Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated With Immune Effector Cells International Myeloma Foundation Leukemia and Lymphoma Society Multiple Myeloma Research Foundation New England Journal of Medicine article: Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma Transplantation and Cellular Therapy article: Overcoming Barriers to Referral for Chimeric Antigen Receptor T Cell Therapy in Patients With Relapsed/Refractory Diffuse Large B Cell Lymphoma Learn more about CAR T-cell therapy and risk evaluation and mitigation strategies (REMS). To discuss the information in this episode with other oncology nurses, visit the ONS Communities. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From Today's Episode “Just like with anything we do in oncology, there is a lot of education that is required. The same navigators that take care of our patients through the transplant and cellular therapy process, we have similar cellular coordinators that were part of the focus group. These navigators were critical to start the education and provide effective resources that were reinforced throughout the treatment.” Timestamp (TS) 09:00 “The nurses and coordinators play a huge role during the transition of care. Not only do they help with coordinating appointments, but also the scheduling of tests and coordinating with the referring team. I heard a lot in the focus groups about the nurses communicating from inpatient to outpatient, and also coordinating from center to center.” TS 10:22 “Patients can get really nervous when they're feeling sick. I explain it to them like, “You know how you get a flu shot, and you might get a little reaction as we're training your immune system to provide immunity? Well, it's like that, but way worse.' So, you can get really sick feeling and achy from this, and so that psychosocial support is super important.” TS 18:16 “It takes a lot of burden on the patient, caregiver, and the nurse to really be astute to those symptoms and intervene. We do provide wallet cards to patients. We educate the emergency department staff. We also heard about the infection monitoring and caregiver support is absolutely critical. Fortunately, the symptom management has become quite standardized, which really affords the nurses more autonomy to intervene more efficiently.” TS 20:46 “The nurses found for education a teach-back tool to be quite useful. One of the nurses mentioned asking the patient questions such as, ‘What will you do when you have a fever? Tell me what you do,' and “What do you understand from what the doctor just told you?' And so that was just kind of a way that they could go back and forth with the educational process and really understand what the patients understood.” TS 25:46

Dr. John Sweetenham and Dr. Marc Braunstein discuss the role of maintenance therapy in high-risk multiple myeloma, advances in myelodysplastic syndromes in the COMMANDS study, the promise of bispecific antibodies in the pivotal EPCORE NHL-1 in relapsed/refractory large B-cell lymphoma, and improving outcomes for patients with chronic lymphocytic leukemia in the CAPTIVATE trial.  TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the associate director for cancer network 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. Marc Braunstein, a hematologist and oncologist at the NYU Perlmutter Cancer Center. Today, we'll be discussing key posters and oral abstracts highlighting advances in hematologic malignancies that will be featured at the 2023 ASCO Annual Meeting.   You'll find our full disclosures in the transcript of this episode, and disclosures of all guests on the ASCO Daily News Podcast are available on our transcripts at asco.org/DNpod.  Dr. John Sweetenham: So, Marc, thanks for returning to us and coming to join us on the podcast today. Dr. Marc Braunstein: Thanks for inviting me back. Dr. John Sweetenham: I'd like to start out with Abstract 8001. This is a study which is addressing the role of maintenance therapy in patients with high-risk multiple myeloma. Could you take us through this study and the key take-home points that you think are the most important ones? Dr. Marc Braunstein: Sure, absolutely. So, the first abstract that we're going to discuss is an oral abstract being presented by Dr. Nooka regarding maintenance therapy in high-risk multiple myeloma patients. Outcomes of patients with multiple myeloma are clearly improving, yet those with high-risk cytogenetic abnormalities, which represent about 10-20% of all multiple myeloma, tend to have poorer survival, and worst among these are those with what's called ultra-high-risk or double-hit multiple myeloma who have more than 1 high-risk cytogenetic abnormality. So, this study looked at maintenance therapy following stem cell transplantation in 26 high-risk patients, about 59% of whom had double hit disease, representing very high-risk disease. This was a phase II study looking at using carfilzomib, pomalidomide, and dexamethasone in high-risk multiple myeloma patients who achieved at least a partial remission following stem cell transplant. There were 26 patients enrolled. The median age was 60. Of note, about 59% of patients were Black, which is important because these patients tend to be historically underrepresented in studies. And what they found was that at study entry, about 24% of patients were in a complete remission or better, and that deepened to 79% while on the study. And the median time to best response was 2 months, which is fairly brisk. With a median follow-up of about 26 months, the 36-month progression-free survival was 63%, and the overall survival was 72%, which is impressive, again in the context of patients who have very high-risk disease. So, although it remains to be determined what the optimal regimen or duration of maintenance should be in multiple myeloma, clearly, combination therapy is effective and should be used in patients who have high-risk or ultra-high-risk multiple myeloma. Dr. John Sweetenham: Great. Thanks, Marc. So, as you say, I mean, clearly the take-home message is around the effectiveness of this type of maintenance therapy. I just have a couple of quick follow-up questions for you. The first of those is, where do you see this going next? I mean, in your opinion, what would be the next logical study with this combination or similar combinations? And then secondly, what do you see on the horizon for those patients with very high-risk myeloma, particularly the double-hit population that you just mentioned? Dr. Marc Braunstein: It's a paradigm in multiple myeloma that combination therapy tends to be more effective as long as we're able to manage the adverse events that come with additional combinations. And we've been able to succeed in that regard with quadruplet regimens, even now that we have monoclonal antibodies that tend to be better tolerated and more targeted in nature. In terms of maintenance therapy, single-agent lenalidomide has been the long-standing agent of use for the majority of patients. But we now understand that the combination of an immunomodulator like lenalidomide and a proteasome inhibitor like bortezomib or carfilzomib is more effective for patients with higher risk disease.   We also have data from various upfront studies of quadruplet regimens, such as the FORTE study, which looked at carfilzomib and lenalidomide maintenance after transplant that shows that we can improve progression-free survival in all comers with multiple myeloma following transplants. So, I think down the road we're going to be looking at more use of combination therapies and maintenance. And as far as for high-risk patients, whether that's going to be using monoclonal antibodies in maintenance or combination proteasome inhibitors and immunomodulators or even other immunotherapies like bispecific antibodies as maintenance in the future remains to be determined, but clearly, for high-risk patients, we should be using combination therapies. Dr. John Sweetenham: Thanks, Marc. Let's change gears a little now and take a look at Abstract 7003, which addresses patients with myelodysplastic syndrome. This study addresses the efficacy and safety results from a study of luspatercept versus epoetin alfa in low-risk myelodysplastic syndrome. I wonder if you could describe this study and the results to us and maybe also for the benefit of our listeners, just mention quickly the mechanism of action of the experimental agent here.  Dr. Marc Braunstein: This is an oral abstract being presented by Dr. Garcia-Manero looking at a phase 3 study, as you mentioned, called the COMMANDS study, and this is looking at an agent called luspatercept in patients with low-risk myelodysplastic syndrome (MDS). So, patients with MDS can have inferior quality of life and survival when they become transfusion dependent. An earlier study called the MEDALIST study, which was published in the New England Journal of Medicine in 2020, randomized low-risk or intermediate-risk patients with MDS who were refractory or unlikely to respond to erythropoietin stimulating agents to either luspatercept, which is an agent that binds to TGF-beta family members and helps stimulate erythropoiesis. Patients were randomized in the MEDALIST study to luspatercept or placebo. And that study showed that luspatercept could improve a degree of anemia and lead to transfusion independence in certain patients. So, the COMMANDS study is a randomized controlled study that randomized 354 patients with low-risk MDS who were transfusion dependent and naive to an erythropoietin stimulating agent to receive either luspatercept or the erythropoietin stimulating agent erythropoietin alfa with the primary endpoint of transfusion independence at some time between 12 to 24 weeks. So, patients were randomized 1:1 to receive either luspatercept or epoetin alfa, and the primary endpoint again was transfusion independence. So, 354 patients were randomized in the study and the median treatment durations were 42 weeks of luspatercept and 27 weeks of epoetin alfa. And transfusion independence occurred in greater quantity in the patients who got luspatercept. For example, in the patients who received luspatercept at 8 weeks, transfusion independence was achieved in 74 versus 51% in the epoetin alfa group. So, in terms of treatment-related adverse events, they were fairly similar between the groups and consistent with the classes -  they were reported in 30% in the luspatercept group and 17% in the erythropoietin group, with no difference in patients who progressed to acute myeloid leukemia.  So, I think when it comes to MDS in low-risk patients, it's really important to preserve their quality of life by limiting their transfusion burden. And I think this study demonstrates that luspatercept continues to be an important part of the management in these low-risk patients. And whether or not you would start a patient with low-risk transfusion-dependent MDS on an erythropoietin stimulating agent or luspatercept is really addressed by this study showing that you can achieve greater rates of improvement in anemia and transfusion independence with luspatercept.  Dr. John Sweetenham: Great. Thanks, Marc. A really interesting study. And I do have one question for you about this study, which I think will make it clear to you that I am an expert neither in myelodysplastic syndrome nor in erythropoiesis. But my question is based on the mechanism of action. Is there any rationale for combining these 2 agents in future studies?  Dr. Marc Braunstein: Yes, it would potentially make sense to use 2 synergistic mechanisms to improve erythropoiesis. We would have to see what the potential for adverse events are. I think epoetin alfa tends to be a fairly low burden in terms of its side effect profile. Luspatercept can have some potentially dose-limiting side effects, such as GI side effects, but you can make dose adjustments to both of these medications. So we may need to find the correct doses of either of them in combination. But from a theoretical standpoint, it makes sense that these could potentially be synergistic, especially in patients who are likely to respond to erythropoietin by having a baseline lower erythropoietin level. Dr. John Sweetenham: Okay, let's move on in another change of gear now. And for the rest of the podcast, we're going to be talking about some studies in lymphoid malignancy, beginning with Abstract 7535, which is a follow-up of the phase 2 CAPTIVATE study which now has significantly extended follow-up from the original report. So Marc, can you walk us through this study and the outcomes to date? Dr. Marc Braunstein: Absolutely. So this is a poster being presented by Dr. Barr and it is looking at CLL, which is a field that is really moving away from chemotherapy for newly diagnosed patients, thanks to the development of novel targeted agents. The CLL14 trial, which was published in the New England Journal of Medicine in 2019, showed that fixed-duration venetoclax plus obinutuzumab improved progression-free survival and rates of negativity of minimal residual disease, or MRD, when compared to chlorambucil and obinutuzumab. So building on the success of that study, combining a monoclonal antibody and a BCL2 inhibitor, the CAPTIVATE study is a phase II study, which examines venetoclax with ibrutinib, the BTK inhibitor, and previously untreated CLL. So it's kind of combining 2of the novel targeted therapies in a fixed duration, similar to what was done in the CLL14 study where patients received 1 year of therapy and then stopped treatment.   So in the CAPTIVATE study, 154 patients were enrolled. This was a phase 2 study that included about 56% of higher-risk patients who had unmutated IGHV, and the median time on the study was 50 months, with a CR rate of 58% at a 4-year follow-up and an overall response rate of 96%, which is quite high, especially considering that more than half of patients had high-risk disease. The progression-free survival was 79% and the overall survival rate was 98% at 4 years. And when they looked at patients who had undetectable minimal residual disease, the 4-year overall survival rate was 100%, which also suggests that MRD can help serve as a predictive marker of longer-term survival. So I think we have to also consider what the side effects are of combining these 2 agents and the most common adverse events were hematologic, which is expected based on what we know about the 2 classes. So I think the implication of the study is that giving 2 oral agents for a fixed period of treatment for 12 cycles is a rational approach that may spare patients indefinite therapy and can lead to positive outcomes, including in patients who have high-risk features with CLL.  Dr. John Sweetenham: Yeah, the other interesting observation that was made in the abstract, which I found to be really encouraging, was the fact that a number of these patients apparently have been re-treated successfully upon progression with ibrutinib again, which seems to be somewhat reassuring as well.  Dr. Marc Braunstein: That's right. There were 4 patients who started re-treatment in the study and perhaps we'll see the outcomes of that small subgroup are at the poster presentation. But I think when we discuss fixed-duration treatment, it also opens the door to potentially re-challenging patients when they relapse. We know that when we stop single-agent BTK inhibitors, which are historically given indefinitely in patients with CLL, those patients who stop, many will relapse, but you can potentially re-challenge them with the BTK inhibitor. So this study with the CAPTIVATE trial gives us some liberty to discontinue therapy, but also considering re-challenging upon relapse.   Dr. John Sweetenham: Yeah, absolutely. Moving on to aggressive B-cell lymphoma, now, the next abstract I'd like to discuss with you is Abstract 7525. I find this one particularly interesting as the continued excitement around CAR T cell therapy for relapsed aggressive lymphoma remains high at the moment. It's intriguing that t cell-engaging antibodies also have been reported, at least, to have remarkable activity in this set of diseases. So can you take us through Abstract 7525 and what they're reporting?  Dr. Marc Braunstein: Absolutely. Bispecific antibodies represent an emerging field in multiple hematologic malignancies, and this is a class of antibodies that bind to both the tumor cell as well as T-cells, and activate T-cell immunity against the tumor cell. So epcoritamab is a bispecific antibody that binds to CD3, which is expressed on T cells, and CD20, which is expressed on B cells. And Thieblemont et al published results in the Journal of Clinical Oncology last year in a phase I/2 study that looked at epcoritamab in patients with diffuse large B cell lymphoma following 2 prior lines of therapy, and this was given subcutaneously until progression of disease. In that study, at a median follow-up of about 11 months, the overall response rate was 63% with 39% complete remissions.   So the EPCORE NHL-1 study, which is being presented at this year's ASCO meeting, is presenting the updated results of that study looking at patients with diffuse large B cell lymphoma that includes a small population as well of patients with high-grade B cell lymphomas and primary mediastinal B cell lymphomas who had at least 2 prior lines of therapy. In this presentation, 157 patients were included in this study, and 61% had primary refractory disease, and actually, 39% had prior CAR T-cell therapy, of whom 75% progressed within 6 months. So these were patients who were not only refractory to treatment but also had prior T-cell therapy.   So at a median follow-up of 20 months, the overall response rate was 63% and the complete response rate was again about 39%, and the median duration of complete remission was 21 months. In terms of overall survival, the median was about 19 months, which is substantial for this group of patients who really wouldn't be expected to respond very well to conventional therapies.   As we know, T-cell-engaging therapies, such as these bispecific antibodies or CAR T-cells have the potential risk for certain immune-related adverse events, including cytokine release syndrome or icons, and a neurologic syndrome related to the therapy. And it's worth noting that the CRS in this study was predominantly low-grade. There were only 3% of patients who had grade III CRS, and 9 patients, or 6% had grade I to II icons. I think that also reflects how we're better managing those side effects and intervening earlier. So I think the results are impressive from the standpoint of the population studied, who were quite refractory to treatment and show relatively high rates of response. In fact, the median overall survival was not reached in the overall population.   So I think what we take away from this abstract is that bispecific antibodies are going to play a vital role in the relapse-refractory setting for large cell lymphoma and may also offer an alternative to patients who aren't necessarily fit for CAR T-cell therapy, which plays a vital role in patients who are both refractory to first-line therapy or relapse-refractory to subsequent disease. So these are very encouraging results, and I'm sure we'll see randomized data as well in the future, further supporting the use of bispecific antibodies like epcoritamab.  Dr. John Sweetenham: Yeah, I agree. Thanks, Marc. I think that's a great summary. And it's particularly exciting to me that the investigators were able to achieve this kind of level of response and progression-free survival with a subcutaneous treatment. It's really quite remarkable and really exciting to see that.  We're going to wind up with our final abstract today, which is looking at the utilization of circulating tumor DNA in, again, in patients with aggressive B cell lymphoma. This is Abstract 7523, so maybe you could walk us through this one, Marc.  Dr. Marc Braunstein: Absolutely. So this is a poster being presented by Dr. Herrera looking at a, I guess you could call it a biomarker in the blood using circulating tumor DNA in patients with newly diagnosed diffuse large B cell lymphoma in the POLARIX study. So the results of the phase 3 POLARIX study were published last year in the New England Journal of Medicine and showed improvement in progression-free survival with the addition of these anti-CD79b antibody polatuzumab to standard R-CHOP chemotherapy compared to R-CHOP alone. And this study actually led to the approval of first-line treatment that includes polatuzumab.   In the abstract being presented by Dr. Herrera, the investigators looked at the value of circulating tumor DNA as a potential marker to serve as a guide for prognosis and predicting longer-term responses, particularly when the blood is cleared of circulating tumor DNA. So the study involved 654 patients who had ctDNA results both at baseline and then with longitudinal assessment, and they used an assay called the CAPP-Seq assay to assess circulating tumor DNA and assess for its clearance. In the study, undetectable circulating tumor DNA was achieved in 57% of patients who got the polatuzumab R-CHP combination and 59% of the patients who got R-CHOP by cycle 5 and then 6% in the polatuzumab group at 67% in the R-CHOP group.  So the rates of circulating tumor DNA clearance were similar between the 2 arms. But what's notable is that patients in the polatuzumab arm who achieved a complete response at the end of treatment plus cleared their circulating tumor DNA had superior progression-free and overall survival compared to patients who achieved a CR but retained circulating tumor DNA in their blood.   And this has implications because it might help gauge, for example, if patients may need additional cycles to clear the circulating tumor DNA, although we still need more data to answer whether that's necessary or not. And it may help serve as a predictive marker for longer-term remission, particularly in patients who perhaps have higher risk factors at baseline. So I don't think this is necessarily ready for primetime to use in clinical practice, but it is intriguing to know that we could finally have a tumor-specific biomarker in the blood to help monitor patients and potentially predict their longer-term remissions.  Dr. John Sweetenham: Thanks, Marc. I agree. Great summary, and obviously there's still something to learn about the kinetics of the response and so on. And also, I suppose it raises the question of whether those patients who still have detectable levels should be switched at the end of therapy to some kind of preemptive second-line therapy. And these are obviously all questions for the future, but it's going to be very interesting to watch this space, I think, and see how this story develops. Dr. Marc Braunstein: Absolutely. And my colleagues in the solid tumor space are already using circulating tumor DNA, for example, in colon cancer, to help with surveillance. So perhaps this could be a tool to use to predict relapse also in patients who are on surveillance after their treatment. But again, as you alluded to, we need more data to address that.  Dr. John Sweetenham: Well, thanks so much, Marc, for sharing your insights with us today on a really interesting set of abstracts coming up at the June meeting. And thanks for joining us on the ASCO Daily News Podcast. Dr. Marc Braunstein: Thank you for inviting me.  Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in a transcript of this episode. Join us again after the annual meeting for key takeaways on the late-breaking abstracts and other key advances from the ASCO Annual Meeting. And 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 speakers:  Dr. John Sweetenham 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 OncologyResearch Funding (Institution): Janssen, Celgene/BMS

Listen to a soundcast of the April 17, 2023, FDA approval of Omisirge (omidubicel-onlv) to reduce time to neutrophil recovery and infection in patients with hematologic malignancies.

This week we sit down with Alison Gulbis, PharmD, BCOP, Kamakshi Rao, PharmD, BCOP, FASHP, and Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA to discuss their work on the Oncology Workforce Collaborative. Alison is a Clinical Pharmacy Manager at the University of Texas MD Anderson Cancer Center in Houston, TX. She obtained her PharmD at the University of Florida and completed her PGY1 and PGY2 residencies at the Medical University of South Carolina. She has been in clinical practice for 19 years at MD Anderson and manages a team of clinical pharmacy specialists in pediatric hematology/oncology and adult stem cell transplant.Kamakshi is an Interim Director of Pharmacy at the University of North Carolina Medical Center in Chapel Hill. She oversees Adult Ambulatory and Acute Clinical Services as well as the hospital's academic enterprises, including resident and student training programs.  Additionally, she leads the department's growing efforts around diversity, equity, and inclusion. She spent 20 years in direct patient care, working with patients undergoing bone marrow transplants at the North Carolina Cancer Hospital before moving into her current role.Zahra is a Clinical Pharmacy Manager in the Division of Hematologic Malignancies and Cellular Therapeutics at the University of Kansas Health System (TUKHS). She earned her PharmD and MBA from the UMKC School of Pharmacy and the Henry W. Bloch School of Management. She completed residency training at The Ohio State University Medical Center and The Huntsman Cancer Institute at the University of Utah. She has been a board-certified oncology pharmacist since 2012. In 2022, she was the recipient of the ASTCT Pharmacy Special Interest Group Lifetime Achievement Award and ASCO's 40 Under 40 in Cancer award.You can read more here: https://accpjournals.onlinelibrary.wiley.com/doi/10.1002/jac5.1693

When standard chemotherapy wasn't working for one patient, a blend of two remarkable therapies – CAR-T and CRISPR – trained the immune system to exterminate the cancer. Guests include patient Katie Kopp and Dr. Joseph McGuirk, hematologist and medical oncologist and the Division Director of Hematologic Malignancies and Cellular Therapeutics at The University of Kansas Cancer Center.

In the second episode of this Hematopoiesis Bench to Bedside series, Dr. Manuel Espinoza-Gutarra has conversations with Dr. Aaron Mitchell, Dr. Yousuf Zafar (@yzafar), Dr. Aju Mathew, and Dr. Nandita Khera (@khera_nandita), experts in the field of financial toxicity in cancer patients, who offer different perspectives regarding the impact of the financial costs of modern anticancer treatment puts on patients, how should we adequately measure it and how to tackle it.Music: “Somebody New” RYYZN (www.toneden.io/ryyzn/post/somebody-new-copyright-free). Licensed under Creative Commons: By Attribution 3.0 creativecommons.org/licenses/by/3.0/.

Go online to PeerView.com/XZA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. This unique video-based activity will offer learners a window into practice by featuring a series of expert-led lectures that will seamlessly link the latest scientific evidence on CAR-T therapy across a range of hematologic malignancies with panel-based insights on clinical decision-making. Each session will include a Tumor Board segment designed to reflect real-world clinical experiences and decision challenges, from identifying patient candidates to appropriate follow-up and the management of a unique spectrum of adverse events. Upon completion of this CE activity, participants will be able to: Evaluate the latest clinical evidence on the safety and efficacy of chimeric antigen receptor (CAR)-T cell therapies in patients with hematological malignancies across existing and potential future indications; Adopt best practices for integrating CAR-T therapy into the care of patients with hematologic malignancies, including appropriate patient selection, referral to specialized treatment centers, clinical trial enrollment, and provision of post-treatment follow-up care; and Develop appropriate adverse event management strategies for patients with hematological malignancies who are experiencing toxicity (eg, cytokine release syndrome or neurotoxicity) while receiving CAR-T therapy.

Go online to PeerView.com/XZA860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. This unique video-based activity will offer learners a window into practice by featuring a series of expert-led lectures that will seamlessly link the latest scientific evidence on CAR-T therapy across a range of hematologic malignancies with panel-based insights on clinical decision-making. Each session will include a Tumor Board segment designed to reflect real-world clinical experiences and decision challenges, from identifying patient candidates to appropriate follow-up and the management of a unique spectrum of adverse events. Upon completion of this CE activity, participants will be able to: Evaluate the latest clinical evidence on the safety and efficacy of chimeric antigen receptor (CAR)-T cell therapies in patients with hematological malignancies across existing and potential future indications; Adopt best practices for integrating CAR-T therapy into the care of patients with hematologic malignancies, including appropriate patient selection, referral to specialized treatment centers, clinical trial enrollment, and provision of post-treatment follow-up care; and Develop appropriate adverse event management strategies for patients with hematological malignancies who are experiencing toxicity (eg, cytokine release syndrome or neurotoxicity) while receiving CAR-T therapy.

Dr. Amit Mehta, an oncologist joins the podcast to discuss topics in medical oncology for in this edition of the PV Roundup specialist spotlight.

“It's actually the nurse who most often first identifies the subtle signs of sepsis in patients. Trust your clinical judgement,” ONS member Laura Zitella, MS, RN, ACNP-BC, AOCN®, nurse practitioner at the University of California, San Francisco, told listeners during a conversation with Stephanie Jardine, BSN, RN, oncology clinical specialist at ONS. Zitella explained the nursing and management considerations for febrile neutropenia and what to do if it transitions into sepsis. This episode is part of a series about oncologic emergencies; the previous episodes are also linked below. You can also earn free NCPD contact hours after listening to this episode by completing the evaluation linked below. Music Credit: "Fireflies and Stardust" by Kevin MacLeod Licensed under Creative Commons by Attribution 3.0 Earn 0.5 contact hours of nursing continuing professional development (NCPD) by listening to the full recording and completing an evaluation at myoutcomes.ons.org by August 12, 2024. The planners and faculty for this episode have no relevant financial relationships with ineligible companies to disclose. ONS is accredited as a provider of NCPD by the American Nurses Credentialing Center's Commission on Accreditation. Episode Notes Complete this evaluation for free NCPD. Previous Oncology Nursing Podcast episodes on oncologic emergencies Clinical Journal of Oncology Nursing articles: Sepsis: Symptoms, Assessment, Diagnosis, and the Hour-1 Bundle in Patients With Cancer NEWS Scoring System: Use in Hematologic Malignancies and Cellular Therapeutics Patient Populations Febrile Neutropenia: Decreasing Time to Antibiotic Administration in a Community Hospital Emergency Department ONS book: Understanding and Managing Oncologic Emergencies: A Resource for Nurses (third edition) ONS courses: Oncologic Emergencies Treatment and Symptom Management—Oncology RN Essentials in Oncologic Emergencies for the Advanced Practice Provider ONS Huddle Cards™ International Guidelines for Management of Sepsis and Septic Shock National Comprehensive Cancer Network guidelines on prevention and treatment of cancer-related infections Sepsis Alliance Surviving Sepsis Campaign To discuss the information in this episode with other oncology nurses, visit the ONS Communities. To provide feedback or otherwise reach ONS about the podcast, email pubONSVoice@ons.org. Highlights From Today's Episode “We know that fever and neutropenia in combination needs to be treated immediately. This is a high-risk oncologic emergency. Our patients who have febrile neutropenia are at very high risk of having a severe infection or sepsis.” Timestamp (TS) 03:44 “Patients with cancer are at an increased risk for infection because of the inherent immunosuppression of the cancer itself and also the treatment.” TS 08:28 “There are some very, very basic things that patients can do [to decrease risk for infection]. The most important is good handwashing. I explain to patients that your skin is the best barrier against getting an infection. If there's no break in the skin, then infection cannot get in. So, if your hands get contaminated and you wash them before you touch your eyes or your mouth or your nose, then that is a good way to prevent infection.” TS 11:42 “Even if a patient does everything perfect, most of the time when you're neutropenic, the infections that develop come from endogenous organisms. So, our body is colonized with probably 10 times as many microbes as human cells, and when the immune system is suppressed, it allows these organisms sometimes to cause infection. So, it's very important for patients to know that if they have signs of infection that they should let us know so that we can start immediate treatment to treat the infection.” TS 14:01 “If patients are higher risk or they have any organ dysfunctions, or other symptoms—like they're unwell, nausea, vomiting, diarrhea, any symptoms like that—they should be admitted to the hospital, and we would initiate IV antibiotics.” TS 17:37 “It's actually the nurse who's most often the person that first identifies sepsis in patients, so I think it's really important to trust your clinical judgement. When you look at a patient, it's really easy to tell when something is wrong. When they're starting to breathe too heavy or they're a little bit off and they're starting to get some altered mental status, or suddenly their heart rate is elevated for no reason even though they're just lying in bed. So, nurses are really positioned and are most often the ones who first pick up on these subtle signs.” TS 27:17

How many COVID-19-related deaths could have been prevented by vaccination? Find out about this and more in today's PV Roundup podcast.