Episoder
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Episode Overview
For the second time in two decades, a phase 3 trial has shown a statistically significant improvement over R-CHOP in newly diagnosed diffuse large B-cell lymphoma (DLBCL). In this episode, Eddie, Raj, and Ashwin sit down with Professor Charles Herbaux to unpack the data, debate the clinical implications, and ask the question that's on every hematologist's mind: is this enough to change practice?
Background: Setting the Stage for Tafasitamab
Before diving into frontMIND, the episode provides context on tafasitamab, a CD19-targeting monoclonal antibody
L-MIND (Phase 2 — relapsed/refractory DLBCL):
81 patients with R/R DLBCLORR 58%, complete response rate 41%Established activity of tafasitamab + lenalidomide in the relapsed settinghttps://pubmed.ncbi.nlm.nih.gov/32511983/First-MIND (Phase 1b — frontline DLBCL, IPI 2–5):
66 patients randomized: tafa-R-CHOP (n=33) vs. tafa-len-R-CHOP (n=33)ORR: 75.8% vs. 81.8%, respectivelySerious treatment-emergent adverse events: 42.4% vs. 51.5%Provided the signal (and the safety caution) to move to phase 3https://pubmed.ncbi.nlm.nih.gov/37369099/The frontMIND Trial
Design: Phase 3, double-blind, placebo-controlled randomized trial
Intervention: R-CHOP + tafasitamab (12 mg/kg IV days 1, 8, 15 per cycle) + lenalidomide (25 mg/day, days 1–10 per cycle)Control: R-CHOP + placebosGCSF mandatory (given double-blind design); VTE prophylaxis (heparin or aspirin) mandatory given lenalidomideEnrollment: May 2021 – March 2023; 899 patients randomizedPrimary endpoint: Investigator-assessed progression-free survival (PFS)Patient Population:
Age 18–80; DLBCL or high-grade B-cell lymphoma, IPI 3–5Median age: 65 years96% advanced stage; 54% bulky disease; 31% ECOG PS 2; 82% elevated LDH55% IPI 3 / aaIPI 2; 43% IPI 4–5 / aaIPI 38% double/triple hit — a high-risk subgroup included despite R-CHOP being the controlBroad histologic inclusion: transformed lymphoma, grade 3B FL, T-cell/histiocyte-rich LBCL, EBV+ DLBCL, ALK+ LBCL, HHV8+ DLBCL Note: On retrospective central review, ~7% of patients had a different histology (roughly half had FL grade 1–3A), underscoring the diagnostic challenges in DLBCL~40% received pre-phase steroids; 8% rituximab; 4% vincristine prior to cycle 1Key Efficacy Results
(Primary analysis at median follow-up 35.2 months)
| Endpoint | Tafa-Len-R-CHOP | R-CHOP | HR / p-value | 2-year PFS | 71.1% | 62.9% | HR 0.75, p=0.0194
| 3-year PFS | 67.3% | 60.7% | ~6.6% absolute difference
| Overall Survival | — | — | HR 0.85, p=0.27 (immature)Points of Discussion:
Absolute PFS benefit at 2 years: ~8.2%; at 3 years: ~6.6% — a modest but statistically significant improvementOS curves cross early, then separate slightly from ~18 months; data remain immatureEarly censoring observed: ~17% (intervention) and ~14% (control) censored by 9 months — raises questions about off-protocol therapySubgroup consistency: PFS benefit appeared consistent across prespecified subgroups; specific subgroups discussed in the episodeSafety
Adverse Event | Tafa-Len-R-CHOP | R-CHOP
| Fatal treatment-emergent AEs | 6% (26 pts) | 4% (17 pts)
| Diarrhea (any grade) | 25% | 17%
| Febrile neutropenia | 17% (incl. 1 death) | 13%
| Grade ≥3 anemia | 24% | 17%
| Grade ≥3 thrombocytopenia | 27% | 14%The addition of tafasitamab and lenalidomide to R-CHOP adds meaningful hematologic toxicity, particularly thrombocytopenia and anemia, as well as diarrhea and febrile neutropenia.
Key Discussion Points from the Episode
Did the early-phase L-MIND and First-MIND data justify bringing tafasitamab into the front-line setting, and was tafa-len-R-CHOP the right intervention arm to take forward?Is R-CHOP the appropriate control for a patient population that includes 8% double/triple hit lymphoma?What are the implications of using investigator-assessed PFS as the primary endpoint — and how critical is effective blinding to the integrity of that endpoint?How do we interpret the early OS curve crossing and currently non-significant OS benefit?Is the ~8% absolute PFS improvement at 2 years clinically meaningful enough to change practice — particularly given the added toxicity?How should we think about patient selection: who would you prioritize for tafa-len-R-CHOP over standard R-CHOP in clinical practice?What does frontMIND mean for the DLBCL treatment landscape alongside polatuzumab-R-CHP (POLARIX)?Resources & Further Reading
frontMIND trial: Lenz et al. Lancet. https://pubmed.ncbi.nlm.nih.gov/42217458/POLARIX: Tilly H, et al. NEJM 2022About BloodCancerTalks
BloodCancerTalks is a medical education podcast hosted by Raj, Ashwin, and Eddie, dedicated to the latest advances in hematologic malignancies. New episodes available wherever you listen to podcasts.
Follow us on X/Twitter for episode updates and hematology/oncology content.
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In this episode, Raj, Ashwin, and Eddie sit down with Dr. Vincent Rajkumar — Professor of Medicine at Mayo Clinic and Chair of the ECOG Myeloma Committee — for a clinically focused conversation on newly diagnosed multiple myeloma. Topics span baseline workup, risk stratification, induction selection, transplant timing, MRD-directed decision-making, and maintenance strategy. The episode closes with a discussion of Open Medicine, a new medical education platform, and Dr. Rajkumar's ongoing advocacy on drug pricing reform.
KEY TOPICS DISCUSSED
Baseline workup: 24-hour urine protein: It is important to obtain 24-hour urine protein with electrophoresis and immunofixation in all newly diagnosed patients — not for diagnosis, but to establish a baseline for long-term management and to distinguish M-protein from albuminuria. In patients where an FLC ratio ≥100 is the sole myeloma-defining criterion, a 24-hour urine Bence Jones protein ≥200 mg is part of the diagnostic threshold for treatment initiation.
Myeloma cast nephropathy: when to biopsy: An involved FLC ≥50 mg/dL supports a presumptive diagnosis of cast nephropathy and treatment can begin without a kidney biopsy. Below this threshold — particularly if renal involvement is the sole myeloma-defining event — kidney biopsy is warranted to exclude light chain deposition disease, MPGN, or other unrelated disorders. It warrants aggressive early treatment (Dara-VCD or Dara-VD), starting even before bone marrow results are available when the diagnosis is clinically clear.
Solitary plasmacytoma [with or without minimal bone marrow involvement]: Patients with ~10% clonal plasma cells technically meet criteria for myeloma, but management in this borderline zone warrants shared decision-making. Solitary plasmacytoma as sitting between smoldering myeloma and overt myeloma on the disease spectrum.
Risk stratification: revised IMWG criteria: The new revision aimed to keep the high-risk designation to ≤15–20% of patients. Del 17p alone confers high-risk status. TP53 mutation without del 17p is exceedingly rare and FISH alone captures the vast majority of cases. All other cytogenetic abnormalities (t(4;14), t(14;16), t(14;20), 1q gain, 1p deletion, biallelic 1p) require at least one co-occurring abnormality to define high risk. Elevated β2-microglobulin with normal renal function is retained as a proxy for high tumor burden.
Emergent indications for treatment initiation: The three situations warranting urgent treatment are acute cast nephropathy (days matter for renal recovery), cord compression (surgery vs. radiation vs. systemic therapy determined by acuity), and hypercalcemia.
Induction regimen selection: For fit, transplant-eligible patients, the preferred induction is a quadruplet — Dara-VRd or Isa-VRd — with dose adjustment as needed. Triplets (Dara-Rd or Isa-Rd) are reserved for those unable to tolerate a quadruplet even with dose reduction. Carfilzomib-based induction is not favored: head-to-head data show no benefit of KRd over VRd in NDMM, and the cost differential is substantial.
Lenalidomide dosing: Starting dose should be individualized: 15 mg for patients over 75, those with small body habitus (<60 kg), or patients of Asian ethnicity. In octogenarians, starting at 5–10 mg is reasonable and allows upward titration based on tolerability and response. The 25 mg starting dose is not appropriate for many real-world patients.
Response depth before transplant: Pursuing deeper response before ASCT by switching induction regimens is not supported by evidence and may result in patients never reaching transplant. All randomized trial data use fixed induction cycles regardless of response depth. In partial responders, high-dose melphalan itself delivers the deeper response — transplant is the treatment!
MRD-directed transplant decision-making: We discussed MIDAS trial, and the main limitation being short follow-up thus far, but it does show limited utility of ASCT in patients who are MRD-negative post-induction.
Maintenance therapy: Doublet maintenance (Dara-len or bortezomib-len) is recommended for high-risk patients and MRD-positive standard-risk patients. Lenalidomide alone is adequate for MRD-negative standard-risk patients. Duration of maintenance is likely more consequential than drug selection — results from the ECOG (len duration) and SWOG (Dara-len vs. len, dara duration) trials are anticipated.
The future of induction therapy: Improving on Dara-VRd (85% PFS at 4 years) will require demonstrating either shorter treatment duration, a potential cure signal (plateau), or replacement of transplant with CAR-T or bispecifics. Trispecific antibodies may eventually replace multi-drug regimens. Trial design must account for the fact that studies starting now may not read out for a decade.
Trial inclusion of high-risk subgroups: Cast nephropathy and plasma cell leukemia are frequently excluded from industry trials due to financial and regulatory risk to sponsors. Dr. Rajkumar argues that real-world observational studies and NIH/philanthropy-funded investigator-initiated trials are the most viable path to evidence generation for these high-risk, underserved populations.
TRIALS & REFERENCES MENTIONED
PERSEUS — Dara-VRd induction + Dara-len maintenance in transplant-eligible NDMM [https://pubmed.ncbi.nlm.nih.gov/38084760/]
IMROZ — Isa-VRd vs. VRd in transplant-ineligible NDMM [https://pubmed.ncbi.nlm.nih.gov/38832972/]
GRIFFIN — Dara-VRd vs. VRd in transplant-eligible NDMM [https://pubmed.ncbi.nlm.nih.gov/37708911/]
MIDAS — MRD-directed transplant decision-making after Isa-KRd induction: https://pubmed.ncbi.nlm.nih.gov/40459097/
ECOG (ongoing) — CybOrD vs. Dara-VD for frontline acute light chain cast nephropathy
ECOG (pending readout) — Fixed vs. indefinite lenalidomide maintenance duration
SWOG (pending readout; DRAMMATIC Trial) — Dara-len vs. len maintenance; duration of daratumumab
Canadian trial — Dara-R(V)D fixed duration vs. indefinite maintenance
Rajkumar SV — AJH 2024: https://pubmed.ncbi.nlm.nih.gov/38943315/
Rajkumar SV & Leung N — Cast nephropathy management: https://pubmed.ncbi.nlm.nih.gov/36990996/; IMWG consensus MCN management: https://pubmed.ncbi.nlm.nih.gov/37414019/
Mayo Clinic series on Solitary plasmacytoma (+/- minimal BM involvement): https://pubmed.ncbi.nlm.nih.gov/42018661/ABOUT OPEN MEDICINE
Open Medicine is an independent, open-access medical education platform co-founded by Dr. Simon Chaudhuri with the goal of bridging the gap between academic expertise and community oncology practice. The platform delivers mobile-first, living clinical algorithms and expert-narrated content — free of paywalls — updated in real time as new data emerge. Dr. Rajkumar serves as a founding circle member, contributing myeloma algorithms and commentary. Follow OpenMedicine on X, LinkedIn and Bluesky:
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Mangler du episoder?
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In this episode, we dive deep into ASH 2025 updates on myeloid malignancies with Dr. Curtis Lachowiez. From the plenary halls of ASH 2025 to long-term follow-up of Aza/Ven/Gilteritinib, we unpack what the latest evidence means for the future of AML management.
1. PARADIGM Trial (Plenary Session, Abstract 6)Fathi A, Perl A, Fell G, et al. Results from PARADIGM – a phase 2 randomized multi-center study comparing azacitidine and venetoclax to conventional induction chemotherapy for newly diagnosed fit adults with acute myeloid leukemia. Blood 2025;146(Suppl 1):6.
https://doi.org/10.1182/blood-2025-6
ClinicalTrials.gov: NCT04801797
2. VICEROY Study – Aza/Ven/Gilteritinib Triplet (Abstract 654)Venetoclax (VEN) and azacitidine (AZA) with gilteritinib (GILT) in patients with newly diagnosed FLT3mut+ AML ineligible for intensive induction chemotherapy: Interim results from the phase 1/2 VICEROY study. Blood 2025;146(Suppl 1):654.
ClinicalTrials.gov: NCT05520567
3. Long-Term Follow-Up of Aza/Ven/Gilteritinib in FLT3-Mutated AML (Abstract 45)Azevedo RS, et al. Long-term follow-up of azacitidine, venetoclax, and gilteritinib in patients with newly diagnosed FLT3-mutated acute myeloid leukemia. Blood 2025;146(Suppl 1):45.
Original publication: Short NJ, Daver N, DiNardo CD, et al. J Clin Oncol 2024;42:1499–1508. https://doi.org/10.1200/JCO.23.01911
ClinicalTrials.gov: NCT04140487
4. PRISM-AML Score (Abstract 453)Lachowiez CA, et al. Prognostic risk integration for survival modeling (PRISM) in newly diagnosed acute myeloid leukemia treated with venetoclax: A multinational retrospective cohort study. Blood 2025;146(Suppl 1):453.
Interactive Calculator: https://prism-aml.com
5. Additional Studies Referenced in Discussion• VIALE-A Trial: DiNardo CD, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med 2020;383:617–629. (NCT02993523)
• VERONA Trial: Randomized study of Aza-Ven vs. Aza vs. placebo in MDS (discussed as a negative study)
• 4-Gene Classifier (mPRS): Bataller A, et al. Prognostic risk signature in patients with AML treated with HMA and venetoclax. Blood Adv 2024;8(4):927–935. https://doi.org/10.1182/bloodadvances.2023011757
• LACEWING Trial: Azacitidine plus gilteritinib vs. azacitidine plus placebo in FLT3-mutated AML (discussed as a negative study)
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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
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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 patients
Link to the NEJM paper: https://www.nejm.org/doi/abs/10.1056/NEJMoa2514663
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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-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 today
2. NEWLY DIAGNOSED MULTIPLE MYELOMA
MajesTEC-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 requirements
MagnetisMM-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 population
LINKER-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 profile
3. RELAPSED/REFRACTORY MULTIPLE MYELOMA
CAMMA-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 T
RedirecTT-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 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 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
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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
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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
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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-materialsHere is the youtube link for FDA proceedings:
https://www.youtube.com/watch?v=5ecyDbK9ezc
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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/
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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.htmlMDS
Abstract 349: https://ash.confex.com/ash/2024/webprogram/Paper194510.html
ATRA in MDS:
https://ash.confex.com/ash/2024/webprogram/Paper200433.html
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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/
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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 -
In this episode, we discussed the top abstracts in lymphoma and CLL presented at the ASH 2024 annual meeting in San Diego with Dr. David A Russler-Germain from Washington University. Here are the key abstracts we discussed:
1. 3 RCTs in Mantle Cell Lymphoma:
a) Update on TRIANGLE: https://ash.confex.com/ash/2024/webprogram/Paper200735.html
b) ENRICH Trial (Continuous Ibrutinib-Rituximab vs CIT [R-CHOP or BR]): https://ash.confex.com/ash/2024/webprogram/Paper199710.html
c) ECOG-ACRIN EA4151 Trial (Auto-HCT vs Rituximab maintenance alone in patients with undetectable MRD after induction): https://ash.confex.com/ash/2024/webprogram/Paper212973.html
2. DLBCL:
a) Update on POLARIX Trial: https://ash.confex.com/ash/2024/webprogram/Paper197938.html
b) Predictive Value of Cell-of-Origin Subtype By Hans Algorithm in DLBCL Patients Receiving Polatuzumab Vedotin: https://ash.confex.com/ash/2024/webprogram/Paper202153.html
c) COALITION trial: https://ash.confex.com/ash/2024/webprogram/Paper204930.html
3. Follicular Lymphoma:
a) Phase 3 inMIND trial (Tafasitamab + R2 vs Placebo + R2): https://ash.confex.com/ash/2024/webprogram/Paper212970.html
b) Loncastuximab tesirine with rituximab in patients with R/R FL: https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00345-4/abstract
4. CLL:
a) AMPLIFY Trial (Fixed-Duration Acalabrutinib Plus Venetoclax with or without Obinutuzumab Versus Chemoimmunotherapy in 1st line CLL): https://ash.confex.com/ash/2024/webprogram/Paper200701.html
5. Hodgkin Lymphoma:
a) Pembrolizumab Maintenance Instead of Auto-HCT for R/R HL: https://ash.confex.com/ash/2024/webprogram/Paper202537.html
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In this episode, we discuss the comeback of belantamab mafadotin in multiple myeloma with Dr. Hang Quach, along with some other important abstracts presented at EHA/ASCO 2024. Here are the studies we discussed:
1. DREAMM-7 RCT: Belantamab-Vd vs Daratumumab-Vd in relapsed MM. https://pubmed.ncbi.nlm.nih.gov/38828933/
2. DREAMM-8 RCT: Belantamab-Pd vs PVd in relapsed MM. https://pubmed.ncbi.nlm.nih.gov/38828951/
3. Long-term follow-up of CASSIOPEIA Trial: https://pubmed.ncbi.nlm.nih.gov/38889735/
4. Update on MRD data from PERSEUS Trial: https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7502
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