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BloodCancerTalks: ASH 2025 Lymphoma Roundup Guest: Dr. Carla Casulo, Associate Professor, Wilmot Cancer Centre, University of Rochester Abstracts Discussed Follicular Lymphoma EPCORE-FL1 (Falchi) - Epcoritamab plus lenalidomide-rituximab (R2) in relapsed/refractory FL Theme: Bispecific antibody combinations in R/R FL; comparing to other approaches   Diffuse Large B-Cell Lymphoma (DLBCL) - Elderly/Unfit Patients MorningSun (Sharman) - Mosunetuzumab monotherapy in patients ≥80 years or chemo-ineligible EPCOR-DLBCL-3 (Vitolo) - Epcoritamab monotherapy in elderly patients R-Pola-Glo - Rituximab-polatuzumab-glofitamab combination in older/frail patients Theme: Single-agent and combination bispecific strategies for elderly and frail DLBCL patients   DLBCL - First-Line Treatment SMART STOP (Westin) - Chemotherapy-free approach using lenalidomide, tafasitamab, rituximab, acalabrutinib (ULTRA regimen) FrontMIND - Tafasitamab-lenalidomide added to R-CHOP Theme: Chemotherapy-sparing and chemo-intensification strategies in newly diagnosed DLBCL   DLBCL - Relapsed/Refractory DALY 2-EU (Borchmann) - Dual CD19/CD20 CAR-T (zamto-cel) versus R-GemOx in transplant-ineligible patients Theme: Expanding CAR-T eligibility; treatment selection in transplant-ineligible R/R DLBCL   Hodgkin Lymphoma SWOG 1826 - 3-year update: Nivolumab-AVD versus brentuximab-AVD HD21 - 5-year update: PET-adapted BrECADD versus BEACOPP Theme: Long-term outcomes and treatment selection in newly diagnosed Hodgkin lymphoma   Burkitt Lymphoma ZUMA-25 (Van Dorp) - Brexucabtagene autoleucel (Brexu-cel) in relapsed/refractory Burkitt Theme: CAR-T therapy for the challenging population of R/R Burkitt lymphoma   Mantle Cell Lymphoma - First-Line   TrAVeRse - Acalabrutinib, venetoclax, rituximab GLOVe - Glofitamab, lenalidomide, venetoclax (high-risk MCL) BOVen - Zanubrutinib, obinutuzumab, venetoclax (older patients) MAVO - Acalabrutinib, venetoclax, obinutuzumab Window-3 - Acalabrutinib-rituximab followed by brexu-cel (high-risk MCL) Theme: Chemotherapy-free combinations in newly diagnosed mantle cell lymphoma

 Join hosts Raj, Ashwin, and Eddie in this episode of Blood Cancer Talks as they welcome Dr. Luciano Costa, the first author of the NEJM manuscript on the MajesTEC-3 RCT, which was presented at ASH 2025. This episode dives deep into the trial's topline findings, capturing the nuances of the patient population, efficacy and safety data, and the future implications for treatment. The episode also examines the comparative efficacy of bispecific T-cell engagers versus CAR-T therapies, along with spirited discussion on the potential for fixed-duration treatment in myeloma care.  Episode Highlights  Main Topics Covered  MajesTEC-3 Trial: Teclistamab-Daratumumab vs. Standard of Care Trial design and patient populationPrimary endpoint: Progression-free survival (PFS)MRD negativity rates and depth of responseOverall survival and safety profileClinical implications for treatment selectionTreatment Selection in Early Relapse Comparing MajesTEC-3 and CARTITUDE-4 patient populationsFramework for choosing between bispecific antibodies vs. CAR T-cell therapyManaging anti-CD38 exposed patientsLink to the NEJM paper: https://www.nejm.org/doi/abs/10.1056/NEJMoa2514663  

Join hosts Eddie, Ashwin, and Raj as they welcome Dr. Michelle Yong and Dr. Gemma Reynolds, academic infectious diseases physicians from the Peter MacCallum Cancer Centre and the National Centre for Infections in Cancer, for an in-depth discussion on cytomegalovirus (CMV) management in immunocompromised hematology patients. Key Topics Covered Fundamentals of CMV Management Distinguishing CMV reactivation from CMV diseaseTreatment thresholds and target viral loadsProphylaxis strategies in non-allograft settingsValaciclovir dosing in general hematology populationsHigh-risk patient populationsFirst-Line Therapies Valganciclovir: advantages, disadvantages, and myelosuppressionFoscarnet: indications and monitoring strategiesTreatment-resistant CMVAllogeneic Transplant Patients High-risk populations and timing of reactivationMonitoring protocols post-transplantRandomized Controlled Trials AURORA Trial: Maribavir vs. Valganciclovir Design: RCT comparing maribavir to valganciclovir for pre-emptive CMV therapy post-allogeneic transplant [https://pubmed.ncbi.nlm.nih.gov/38036487/]NEJM Letermovir Prophylaxis Trial Design: Double-blind, placebo-controlled RCT of letermovir prophylaxis post-allogeneic transplant [https://pubmed.ncbi.nlm.nih.gov/29211658/]Emerging Patient Populations CMV in lymphoma and myeloma patients receiving CAR T-cell therapy and T-cell engaging bispecific antibodiesMonitoring and prophylaxis strategies for novel immunotherapiesImpact of CMV on post-CAR T mortality-https://pubmed.ncbi.nlm.nih.gov/40203190/

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 Covered 1. SMOLDERING MULTIPLE MYELOMA LINKER-SMM1 Phase 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 MYELOMA MajesTEC-5 Phase 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-6 Phase 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-MM4 Phase 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 MYELOMA CAMMA-1 Phase 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 MM Phase 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-1 Phase 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 TOXICITIES CAR 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?

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 Topics 1. Genetic Heterogeneity in B-Cell Lymphomas Complex genetic landscape of DLBCL Implications for treatment strategies Need for personalized approaches   2. Clinical Need for ctDNA in Lymphoma Why ctDNA is needed in aggressive lymphomas: Curative vs. non-curative treatment settings Limitations of current PET imaging Additional prognostic information beyond imaging Risk stratification capabilities Potential to avoid overtreatment Therapy adaptation opportunities   3. Challenges in Lymphoma MRD Assessment Why lymphoma MRD is more complex than other hematologic malignancies: Differences from acute leukemias, CLL, and myeloma Technical challenges specific to lymphoid tumors Lower circulating tumor burden compared to liquid tumors   4. ClonoSEQ Technology Mechanism: Immunoglobulin sequencing approach Advantages: Established platform with regulatory approval Disadvantages: Limited sensitivity in peripheral blood, requires adequate tumor sample   5. CAPP-Seq Technology Full Name: Cancer Personalized Profiling by Deep Sequencing Innovation: Developed ~10 years ago by Dr. Alizadeh's group Mechanism: Targeted sequencing of cancer-specific mutations Advantages: High sensitivity, personalized approach   6. PhasED-Seq Technology Evolution: Next-generation advancement of CAPP-Seq Key Improvements: Enhanced sensitivity and specificity Technical Advances: Phased variant detection   Clinical Data Highlights 1. 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.7000 3. Korean data on prognostic utility of ctDNA: https://ashpublications.org/blood/article/142/Supplement%201/69/501573  

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 Discussed 1. POLARGO Trial - Polatuzumab + R-GemOx vs R-GemOx in R/R DLBCL 2. SUNMO Trial - Mosunetuzumab + Polatuzumab vs R-GemOx in R/R DLBCL 3. STARGLO Trial - Glofitamab + GemOx vs R-GemOx in R/R DLBCL (2-Year Update) 4. EPCORE NHL-5 & NHL-7 - Epcoritamab Combinations in Frontline DLBCL 5. EPCOR-RICE - Epcoritamab + R-ICE in Transplant-Eligible R/R DLBCL 6. LOTIS-7 Trial - Loncastuximab + Glofitamab in R/R DLBCL 7. Additional Studies Mentioned: R-Pola-Glo Frail Study DLBCL Classification

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.22.00843 5. 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-1/534319 9. 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

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/

In this episode, we took a deep dive intro the landscape of menin inhibitors in AML with Dr. Eytan Stein from MSKCC. Here are the key trials and studies we discussed:  ELN 2022 AML Classification https://ashpublications.org/blood/article/140/12/1345/485817/Diagnosis-and-management-of-AML-in-adults-2022Predictors of outcomes in adults with AML and KMT2A rearrangements: https://www.nature.com/articles/s41408-021-00557-6DOT1L inhibitor https://ashpublications.org/blood/article/131/24/2661/37193/The-DOT1L-inhibitor-pinometostat-reduces-H3K79AUGMENT 101: https://ascopubs.org/doi/10.1200/JCO.24.00826Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study: https://ashpublications.org/blood/article/doi/10.1182/blood.2025028357/537139/Menin-inhibition-with-revumenib-for-NPM1-mutatedKOMET-001: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(24)00386-3/abstractSAVE trial: https://ashpublications.org/blood/article/144/Supplement%201/216/530724/Phase-I-II-Study-of-the-All-Oral-Combination-ofKOMET-007: https://library.ehaweb.org/eha/2025/eha2025-congress/4159213/harry.erba.ziftomenib.combined.with.intensive.induction.chemotherapy.2872B329.in.html?f=menu%3D6%2Abrowseby%3D8%2Asortby%3D2%2Amedia%3D3%2Ace_id%3D2882%2Aot_id%3D31560%2Amarker%3D5843%2Afeatured%3D19595MEN1 mutations: https://www.nature.com/articles/s41586-023-05755-9 

In this episode, we discuss the recent proceedings at the FDA ODAC meeting on AQUILA trial in smoldering myeloma and STRAGLO in R/R DLBCL, and provide an update to our audience on some of the clinically relevant data presented from those trials, along with insights from the panelists. Here is the link to the webpage with FDA briefing documents and slides:  https://www.fda.gov/advisory-committees/advisory-committee-calendar/may-20-21-2025-meeting-oncologic-drugs-advisory-committee-05202025#event-materials Here is the youtube link for FDA proceedings:  https://www.youtube.com/watch?v=5ecyDbK9ezc

In this episode, we discussed the management of systemic mastocytosis with Dr. Daniel DeAngelo from the Dana Farber Cancer Institute. Here are the key studies we discussed: Midostaurin https://www.nejm.org/doi/10.1056/NEJMoa1513098?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.govAvapritinibEXLPORER study: https://www.nature.com/articles/s41591-021-01538-9PATHFINDER study: https://www.nature.com/articles/s41591-021-01539-8Bezuclastinib: APEX trial: https://ashpublications.org/blood/article/144/Supplement%201/659/530240/Apex-Part-1-Updated-Assessment-of-BezuclastinibHSCT for Advanced SM: https://ascopubs.org/doi/10.1200/JCO.2014.55.2018

In this episode, we explore the emerging entity of CAR Transgenic T-cell Lymphoproliferative Neoplasms (CTTLN), a rare but important complication of CAR T-cell therapy. Dr. Piers Blombery from Peter MacCallum Cancer Center joins us to dissect two cases from the CARTITUDE-4 trial where patients developed T-cell lymphomas expressing the chimeric antigen receptor following cilta-cel treatment for multiple myeloma. As a bonus, we also briefly discussed Dr. Blombery’s paper on menin inhibitors in UBTF tandem duplicated AML. Here are the papers we discussed:  1. CTTLN cases from CARTITUDE-4: https://pubmed.ncbi.nlm.nih.gov/39938094/ 2. CTTLN case from MSKCC with insertional mutagenesis: https://pubmed.ncbi.nlm.nih.gov/39908432/ 3. Other CTTLN cases in myeloma: https://pubmed.ncbi.nlm.nih.gov/38865661/https://pmc.ncbi.nlm.nih.gov/articles/PMC8417502/ 4. Response and resistance to menin inhibitors in UBTF tandem duplication AML: https://pubmed.ncbi.nlm.nih.gov/38924737/

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

In this episode, we discuss the management of CML with Dr. Hagop Kantarjian from MD Anderson Cancer Center. Here are the key articles we discussed:    1. ASC4FIRST RCT: Asciminib in newly diagnosed CML.  https://pubmed.ncbi.nlm.nih.gov/38820078/   2. 5-year follow-up of ENESTnd RCT (nilotinib):  https://pubmed.ncbi.nlm.nih.gov/26837842/   3. 10-year follow-up of ENESTnd RCT (nilotinib):  https://pubmed.ncbi.nlm.nih.gov/33414482/   4. 10-year follow-up of CML-IV RCT (imatinib):  https://pubmed.ncbi.nlm.nih.gov/25676422/   5. MD Anderson data on low-dose dasatinib (50 mg):  https://pubmed.ncbi.nlm.nih.gov/36054032/ https://pubmed.ncbi.nlm.nih.gov/31553487/   6. CML: 2025 update on diagnosis, therapy, and monitoring:  https://pubmed.ncbi.nlm.nih.gov/39093014/  

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