Episode 66. International Myeloma Society 2025 Annual Meeting Updates with Dr. Alfred Garfall: The Bispecific Bonanza
This episode provides comprehensive coverage of key clinical trial updates from the 2025 International Myeloma Society (IMS) Annual Meeting in Toronto, with special focus on bispecific antibodies and novel immunotherapies across the multiple myeloma disease continuum—from smoldering disease through relapsed/refractory settings. Dr. Alfred Garfall provides expert commentary on study design, efficacy, safety considerations, and clinical implications.Topics Covered1. SMOLDERING MULTIPLE MYELOMALINKER-SMM1Phase 2, open-label study of linvoseltamab monotherapy (200 mg) in patients with high-risk smoldering multiple myeloma by 20/2/20 or PETHEMA criteria, with 2-year treatment duration.Discussion Points:Appropriateness of 2-year treatment duration for precursor conditionEfficacy and MRD-negative ratesSafety considerations in asymptomatic populationPatient selection if available today2. NEWLY DIAGNOSED MULTIPLE MYELOMAMajesTEC-5Phase 2 trial evaluating three teclistamab-daratumumab-based induction regimens in 49 transplant-eligible NDMM patients, followed by auto-transplant and fixed-duration Tec-Dara maintenance.Discussion Points:Post-induction MRD-negativity rates with Tec-DR and Tec-DVRGrade 3-5 infection rates and infection-related deathsQuestionable utility of bortezomib and need for ASCT with 100% MRD-negativityHigh infection prophylaxis requirementsMagnetisMM-6Phase 1/2 dose-finding study of fixed-dose elranatamab 76 mg Q4W with Dara-Len in 37 transplant-ineligible NDMM patients (median age 75 years).Discussion Points:VGPR or better ratesSafety profile including infections and CRS/ICANSRisk of continuous therapy in elderly/frail populationLINKER-MM4Phase 1/2 study of linvoseltamab monotherapy in NDMM with both transplant-eligible and transplant-ineligible pathways, exploring three dose levels (50, 100, 200 mg).Discussion Points:Efficacy of single-agent Linvo in NDMMWhether any NDMM population could achieve long-term control with single-agent BCMA BsAbSafety profile3. RELAPSED/REFRACTORY MULTIPLE MYELOMACAMMA-1Phase 1b randomized dose-expansion study of cevostamab (FcRH5×CD3 bispecific) combined with pomalidomide-dexamethasone in BCMA-naïve patients with median 2 prior lines of therapy.Discussion Points:Efficacy and safety resultsPositioning in treatment paradigmUse before BCMA BsAbs?Sonrotoclax + Dexamethasone in t(11;14) R/R MMPhase 1/2 study of sonrotoclax (next-generation BCL2 inhibitor) plus dexamethasone as an all-oral regimen in patients with t(11;14) R/R MM (median 3 prior lines, ~75% triple-exposed).Discussion Points:Efficacy including response rate and PFSSafety profileFuture of BCL2 inhibitors in t(11;14) myeloma in the era of BsAbs and CAR TRedirecTT-1Phase 2 trial combining teclistamab + talquetamab in 90 heavily pretreated patients with R/R extraosseous extramedullary disease (84% triple-class refractory, 36% penta-refractory, 20% prior BCMA CAR T).Discussion Points:Response rate and durability in difficult-to-treat populationSafety concerns with dual bispecific combinationOff-label use considerations4. CAR T-CELL THERAPY TOXICITIESCAR T Immune-Related Adverse Events (UPenn Study - Ho et al)Large cohort study of 198 patients (125 cilta-cel, 73 ide-cel) examining all adverse events other than CRS, ICANS, IEC-HS, and IECAHT.Discussion Points:Landscape of CAR T IRAEs: incidence, types, and timingRisk factors identified for CirAEsMechanism of toxicities and role of CD4+ CAR T-cellsClinical implications: Should prophylactic corticosteroids be used? What ALC threshold? Optimal dose/duration? Prospective studies needed?
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Episode 65. Circulating Tumor DNA in DLBCL with Dr. Ash Alizadeh and Dr. David Russler-Germain
In this episode of Blood Cancer Talks, hosts Eddie, Ashwin, and Raj welcome two distinguished experts to explore the cutting-edge field of circulating tumor DNA (ctDNA) in B-cell lymphomas. Dr. David Russler-Germain, a lymphoma clinician from Siteman Cancer Centre at Washington University in St. Louis, returns as a familiar voice to the podcast audience. Joining him is Dr. Ash Alizadeh, the Moghadam Family Professor of Medicine, Oncology, and Hematology at Stanford University and leader of the Cancer Genomics Program at Stanford Cancer Institute. Dr. Alizadeh has been instrumental in advancing our understanding of lymphomagenesis and lymphoma genetics over the past two decades, pioneering multiple ctDNA techniques that are revolutionizing cancer care. Together, they discuss the transformative potential of ctDNA technology in B-cell lymphomas, particularly DLBCL, covering everything from the technical evolution of biomarker detection to groundbreaking clinical data that may reshape how we monitor and treat these aggressive cancers. Key Discussion Topics1. Genetic Heterogeneity in B-Cell LymphomasComplex genetic landscape of DLBCLImplications for treatment strategiesNeed for personalized approaches 2. Clinical Need for ctDNA in LymphomaWhy ctDNA is needed in aggressive lymphomas:Curative vs. non-curative treatment settingsLimitations of current PET imagingAdditional prognostic information beyond imagingRisk stratification capabilitiesPotential to avoid overtreatmentTherapy adaptation opportunities 3. Challenges in Lymphoma MRD AssessmentWhy lymphoma MRD is more complex than other hematologic malignancies:Differences from acute leukemias, CLL, and myelomaTechnical challenges specific to lymphoid tumorsLower circulating tumor burden compared to liquid tumors 4. ClonoSEQ TechnologyMechanism: Immunoglobulin sequencing approachAdvantages: Established platform with regulatory approvalDisadvantages: Limited sensitivity in peripheral blood, requires adequate tumor sample 5. CAPP-Seq TechnologyFull Name: Cancer Personalized Profiling by Deep SequencingInnovation: Developed ~10 years ago by Dr. Alizadeh's groupMechanism: Targeted sequencing of cancer-specific mutationsAdvantages: High sensitivity, personalized approach 6. PhasED-Seq TechnologyEvolution: Next-generation advancement of CAPP-SeqKey Improvements: Enhanced sensitivity and specificityTechnical Advances: Phased variant detection Clinical Data Highlights1. Remission Assessment by ctDNA in LBCL on 5 prospective studies of frontline anthracycline-based chemo-immunotherapy: https://pubmed.ncbi.nlm.nih.gov/40802906/2. Prospective validation of end of treatment ctDNA-MRD by PhasED-Seq in DLBCL patients from HOVON-902 clinical trial: https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.70003. Korean data on prognostic utility of ctDNA: https://ashpublications.org/blood/article/142/Supplement%201/69/501573
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Episode 64. Lymphoma Updates from EHA and ICML 2025 with Dr. Adrian Minson
In this episode of Blood Cancer Talks, we have Dr. Adrian Minson from the Peter MacCallum Cancer Centre to discuss the latest developments in lymphoma presented at the recent EHA and ICML meetings in June 2025. The episode focuses primarily on the emerging role of bispecific antibodies in various combinations and treatment settings for diffuse large B-cell lymphoma (DLBCL).Key Clinical Trials Discussed1. POLARGO Trial - Polatuzumab + R-GemOx vs R-GemOx in R/R DLBCL2. SUNMO Trial - Mosunetuzumab + Polatuzumab vs R-GemOx in R/R DLBCL3. STARGLO Trial - Glofitamab + GemOx vs R-GemOx in R/R DLBCL (2-Year Update)4. EPCORE NHL-5 & NHL-7 - Epcoritamab Combinations in Frontline DLBCL5. EPCOR-RICE - Epcoritamab + R-ICE in Transplant-Eligible R/R DLBCL6. LOTIS-7 Trial - Loncastuximab + Glofitamab in R/R DLBCL7. Additional Studies Mentioned:R-Pola-Glo Frail StudyDLBCL Classification
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Episode 63. Management of Follicular Lymphoma with Dr. Gilles Salles
In this episode, we discuss the management of follicular lymphoma with Dr. Gilles Salles from Memorial Sloan Kettering Cancer Center. Here are the articles we discussed: 1. Relevance of Bone Marrow Biopsy in Follicular Lymphoma: https://pubmed.ncbi.nlm.nih.gov/35787017/2. TROG 99.03 (RCT of Systemic Therapy after Involved-Field Radiotherapy in Patients with Early-Stage Follicular Lymphoma): https://pubmed.ncbi.nlm.nih.gov/29975623/3. Long-term follow-up results of RCT comparing early rituximab monotherapy versus watchful waiting for advanced stage, asymptomatic, low tumor burden follicular lymphoma: https://pubmed.ncbi.nlm.nih.gov/40306831/4. RELEVANCE RCT: Lenalidomide plus Rituximab (R2) Versus Rituximab-Chemotherapy Followed by Rituximab Maintenance in Untreated Advanced Follicular Lymphoma: https://ascopubs.org/doi/10.1200/JCO.22.008435. GALLIUM RCT: Obinutuzumab Versus Rituximab Immunochemotherapy in Previously Untreated iNHL. https://pubmed.ncbi.nlm.nih.gov/37404773/https://pubmed.ncbi.nlm.nih.gov/28976863/6. Long-term follow-up of mosunetuzumab in relapsed/refractory FL: https://pubmed.ncbi.nlm.nih.gov/39447094/7. Epcoritamab in relapsed/refractory FL: https://pubmed.ncbi.nlm.nih.gov/38889737/8. Phase 3 inMIND RCT: Tafasitamab plus Lenalidomide and Rituximab for Relapsed or Refractory Follicular Lymphoma: https://ashpublications.org/blood/article/144/Supplement%202/LBA-1/5343199. Long term follow-up results from the Phase 3 PRIMA trial of rituximab maintenance in Follicular Lymphoma: https://ascopubs.org/doi/10.1200/JCO.19.01073
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Episode 62. Unpacking MIDAS Trial in Myeloma with Dr. Meera Mohan
In this episode, we dissect the phase 3 MIDAS trial in newly diagnosed transplant-eligible multiple myeloma with Dr. Meera Mohan. https://pubmed.ncbi.nlm.nih.gov/39841461/https://pubmed.ncbi.nlm.nih.gov/40459097/
This is a podcast on latest advances in the understanding and management of blood cancers. Here, we will bring a wide range of experts within hematologic malignancies to discuss various topics in depth.
Host: Raj Chakraborty, MD from Columbia University, New York, Ashwin Kishtagari, MD, from Vanderbilt University, Nashville, and Edward Cliff, MD, from Harvard University, Boston
Tweet your suggestions and feedback to @rajshekharucms @AshKishtagari @Eddie_Cliff @BloodCancerTalk
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