Blood Cancer Talks

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 population
Primary endpoint: Progression-free survival (PFS)
MRD negativity rates and depth of response
Overall survival and safety profile
Clinical implications for treatment selection

Treatment Selection in Early Relapse Comparing MajesTEC-3 and CARTITUDE-4 patient populations
Framework for choosing between bispecific antibodies vs. CAR T-cell therapy
Managing anti-CD38 exposed patients

Link 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 disease
Treatment thresholds and target viral loads
Prophylaxis strategies in non-allograft settings
Valaciclovir dosing in general hematology populations
High-risk patient populations
First-Line Therapies
Valganciclovir: advantages, disadvantages, and myelosuppression
Foscarnet: indications and monitoring strategies
Treatment-resistant CMV
Allogeneic Transplant Patients
High-risk populations and timing of reactivation
Monitoring protocols post-transplant
Randomized 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 antibodies
Monitoring and prophylaxis strategies for novel immunotherapies
Impact 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 condition
Efficacy and MRD-negative rates
Safety considerations in asymptomatic population
Patient selection if available today

2. 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-DVR
Grade 3-5 infection rates and infection-related deaths
Questionable utility of bortezomib and need for ASCT with 100% MRD-negativity
High infection prophylaxis requirements

MagnetisMM-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 rates
Safety profile including infections and CRS/ICANS
Risk of continuous therapy in elderly/frail population

LINKER-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 NDMM
Whether any NDMM population could achieve long-term control with single-agent BCMA BsAb
Safety profile

3. 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 results
Positioning in treatment paradigm
Use 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 PFS
Safety profile
Future of BCL2 inhibitors in t(11;14) myeloma in the era of BsAbs and CAR T

RedirecTT-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 population
Safety concerns with dual bispecific combination
Off-label use considerations

4. 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 timing
Risk factors identified for CirAEs
Mechanism of toxicities and role of CD4+ CAR T-cells
Clinical 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