Blood Cancer Talks

Episode OverviewFor 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 TafasitamabBefore diving into frontMIND, the episode provides context on tafasitamab, a CD19-targeting monoclonal antibodyL-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 TrialDesign: Phase 3, double-blind, placebo-controlled randomized trialIntervention: 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 EpisodeDid 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 ReadingfrontMIND trial: Lenz et al. Lancet. https://pubmed.ncbi.nlm.nih.gov/42217458/POLARIX: Tilly H, et al. NEJM 2022About BloodCancerTalksBloodCancerTalks 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, 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

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 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 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.htmlb) ENRICH Trial (Continuous Ibrutinib-Rituximab vs CIT [R-CHOP or BR]): https://ash.confex.com/ash/2024/webprogram/Paper199710.htmlc) 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.html2. DLBCL: a) Update on POLARIX Trial: https://ash.confex.com/ash/2024/webprogram/Paper197938.htmlb) Predictive Value of Cell-of-Origin Subtype By Hans Algorithm in DLBCL Patients Receiving Polatuzumab Vedotin: https://ash.confex.com/ash/2024/webprogram/Paper202153.htmlc) COALITION trial: https://ash.confex.com/ash/2024/webprogram/Paper204930.html3. Follicular Lymphoma: a) Phase 3 inMIND trial (Tafasitamab + R2 vs Placebo + R2): https://ash.confex.com/ash/2024/webprogram/Paper212970.htmlb) Loncastuximab tesirine with rituximab in patients with R/R FL: https://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00345-4/abstract4. 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.html5. Hodgkin Lymphoma: a) Pembrolizumab Maintenance Instead of Auto-HCT for R/R HL: https://ash.confex.com/ash/2024/webprogram/Paper202537.html

In this episode, we dive into the management of older adults with Hodgkin Lymphoma with Dr. Andrew Evens. Here are the key articles we discussed: 1. Comparison of ABVD versus Stanford V in older Hodgkin Lymphoma patients: https://pmc.ncbi.nlm.nih.gov/articles/PMC3906856/2. Outcome of older adults ECHELON-1: https://pubmed.ncbi.nlm.nih.gov/34162178/3. Sequential BV-AVD in older adults with Hodgkin Lymphoma: https://pubmed.ncbi.nlm.nih.gov/30179569/4. SWOG S1826 trial (Nivo-AVD vs AAVD in advanced stage classical HL): https://pubmed.ncbi.nlm.nih.gov/39413375/5. S1826 outcomes in older adults: https://ash.confex.com/ash/2023/webprogram/Paper180114.html6. Single-agent BV for older adults with Hodgkin: https://ashpublications.org/blood/article/142/Supplement%201/4435/503453

In this episode, we discuss the management of newly diagnosed transplant in-eligible multiple myeloma with Dr. Timothy Schmidt, with a special focus on IMROZ and BENEFIT RCTs testing quadruplets in this space. Here are the key papers we discussed: 1. MAIA trial (Daratumumab-Lenalidomide-Dexamethasone [DRd] vs Rd in newly diagnosed transplant ineligible myeloma): https://pubmed.ncbi.nlm.nih.gov/34655533/2. S0777 trial (VRd vs Rd in newly diagnosed myeloma [transplant-ineligible or transplant-deferred]): https://pubmed.ncbi.nlm.nih.gov/32393732/3. IMROZ trial (Isatuximab-VRd vs VRd in newly diagnosed transplant-ineligible myeloma): https://pubmed.ncbi.nlm.nih.gov/38832972/4. IFM-2020/BENEFIT trial (Isatuximab-VRd vs Isatuximab-Rd in newly diagnosed transplant-ineligible myeloma): https://pubmed.ncbi.nlm.nih.gov/38830994/5. GEM2017FIT trial (VMP-Rd vs KRd vs Dara-KRd in newly diagnosed transplant-ineligible myeloma): https://ashpublications.org/blood/article/142/Supplement%201/209/500199

In this episode, we discussed the diagnosis and management of polycythemia vera with Dr. Aaron T. Gerds. Here are the shownotes with the key studies discussed: 1. MIPS PV scoring systemhttps://pubmed.ncbi.nlm.nih.gov/31945802/2. REVEAL studyhttps://ashpublications.org/blood/article/143/16/1646/506717/Association-between-elevated-white-blood-cell3. MAJIC PV studyhttps://ascopubs.org/doi/10.1200/JCO.22.01935?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed4. Cyto-PV Studyhttps://www.nejm.org/doi/full/10.1056/NEJMoa12085005. PROUD-PV and CONTINUATION-PV trialshttps://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(19)30236-4/abstract6. RESPONSE clinical trialhttps://www.nejm.org/doi/full/10.1056/NEJMoa14090027. Rusferitide in PVhttps://www.nejm.org/doi/10.1056/NEJMoa2308809?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed