Blood Cancer Talks

BloodCancerTalks: ASCO/EHA 2026 Lymphoma Round-Up with Dr. Thomas Lew
Guest: Dr. Thomas Lew, Peter MacCallum Cancer Centre (Melbourne, Australia) — hematologist specializing in lymphoid malignancies.
In this episode, we break down the biggest lymphoma and CLL data from ASCO and EHA 2026 (Chicago and Stockholm), covering mantle cell lymphoma genomics, bispecific antibodies in DLBCL and follicular lymphoma, a practice-changing (or not) CNS prophylaxis study, transplant-eligible relapsed DLBCL, fixed-duration BTK/BCL2 combinations in CLL, and the first in vivo CAR T data in lymphoma.

1. TRIANGLE: TP53-Mutated MCL Molecular Subgroup Analysis
Molecular subgroup data from the practice-shaping TRIANGLE trial presented by Dr. Marta Grau.
Discussion: Where TP53-mutated MCL stands today, and whether ibrutinib-containing regimens are changing the natural history of this historically dismal subgroup.

2. EPCORE DLBCL-1: Epcoritamab vs. Chemotherapy in R/R DLBCL
Randomized phase 3 trial (n=483) of bispecific antibody epcoritamab vs. investigator's choice chemotherapy (72% R-GemOx, 28% BR) in second-line-or-later, transplant-ineligible R/R DLBCL, presented by Prof. Chris Fox.
Discussion: A PFS benefit without an OS signal, set against a meaningfully higher infection-related mortality — what this means for patient selection and infection mitigation strategies.

3. CNS Prophylaxis in Ultra-High-Risk DLBCL: Does HD-MTX Help?
Pooled analysis of two large multicenter retrospective cohorts (n=1,923 ultra-high-risk patients — CNS-IPI 5–6, testicular/renal/adrenal/breast involvement, or ≥3 extranodal sites), presented by Dr. Matt Wilson (Glasgow) and simultaneously published in JCO. 
Discussion: Whether these data close the door on routine HD-MTX in ultra-high-risk DLBCL, and if any subgroup still warrants prophylaxis.

4. Pola-R-ICE: A Negative Trial in Transplant-Eligible R/R DLBCL
Randomized phase 3 study (4 European cooperative groups; n=294) of polatuzumab vedotin added to R-ICE in transplant-eligible R/R DLBCL, with ASCT/alloSCT/CAR-T permitted as consolidation.
Discussion: Why this trial missed, and what it tells us about the ceiling of intensive salvage chemo-immunotherapy platforms in the CAR-T era.

5. BRUIN-CLL-322: Fixed-Duration Pirtobrutinib + Venetoclax-Rituximab in R/R CLL
Randomized phase 3 trial (n=639) of fixed-duration pirtobrutinib (non-covalent BTKi) plus venetoclax-rituximab (PVR) vs. venetoclax-rituximab (VR, the MURANO-based control) in second-line-or-later R/R CLL.

6. SOUNDTRACK-F1: Surovatamig (CD19 Bispecific) Safety Run-In in Untreated Follicular Lymphoma
Safety run-in from a randomized trial (surovatamig vs. chemoimmunotherapy) in untreated FL meeting GELF criteria, presented by Prof. Chan Cheah — building on EPCORE-FL-1 data presented at ASH.
Discussion: How this CD19-directed bispecific compares to CD20-targeting agents in frontline FL.

7. LB2501: First In Vivo CAR T Data in B-Cell Lymphoma
Late-breaking data from Dr. Lei Fan and Legend Biotech on LB2501, an in vivo CD19/CD20 dual-targeted CAR T therapy — a third-generation, self-inactivating, replication-incompetent lentiviral vector that generates CAR T cells directly in vivo, without lymphodepletion. Builds on the in vivo CAR T myeloma data first presented at ASH and updated at EHA.
Discussion: What these very early but striking data suggest about the feasibility of in vivo CAR T generation in lymphoma, and how it might reshape access to cellular therapy.

BloodCancerTalks is co-hosted by Rajshekhar Chakraborty,  Ashwin Kishtagari and Eddie Cliff. Subscribe wherever you get your podcasts.

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 DLBCL
ORR 58%, complete response rate 41%
Established activity of tafasitamab + lenalidomide in the relapsed setting
https://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%, respectively
Serious treatment-emergent adverse events: 42.4% vs. 51.5%
Provided the signal (and the safety caution) to move to phase 3
https://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 + placebos
GCSF mandatory (given double-blind design); VTE prophylaxis (heparin or aspirin) mandatory given lenalidomide
Enrollment: May 2021 – March 2023; 899 patients randomized
Primary endpoint: Investigator-assessed progression-free survival (PFS)
Patient Population:
Age 18–80; DLBCL or high-grade B-cell lymphoma, IPI 3–5
Median age: 65 years
96% advanced stage; 54% bulky disease; 31% ECOG PS 2; 82% elevated LDH
55% IPI 3 / aaIPI 2; 43% IPI 4–5 / aaIPI 3
8% double/triple hit — a high-risk subgroup included despite R-CHOP being the control
Broad 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 1

Key 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 improvement
OS curves cross early, then separate slightly from ~18 months; data remain immature
Early censoring observed: ~17% (intervention) and ~14% (control) censored by 9 months — raises questions about off-protocol therapy
Subgroup consistency: PFS benefit appeared consistent across prespecified subgroups; specific subgroups discussed in the episode

Safety

 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 2022

About 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.

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:

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)

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