Episode 74. Myeloma Updates from ASCO/EHA 2026 with Dr. Prashant Kapoor

Blood Cancer Talks — Show NotesEpisode: Best of ASCO/EHA 2026 — Multiple Myeloma & AL AmyloidosisGuest: Dr. Prashant Kapoor, MD Professor of Medicine, Mayo Clinic, Rochester, MN Chair, Myeloma, Amyloidosis and Dysproteinemia Group, Mayo ClinicEpisode OverviewIn this episode, the hosts sit down with Dr. Prashant Kapoor to review the highest-impact multiple myeloma and AL amyloidosis data from the 2026 ASCO and EHA annual meetings. The discussion centers on the rapidly shifting relapsed/refractory myeloma landscape, where a wave of phase 3 trials of T-cell engaging immunotherapies (bispecific antibodies and CAR T) have now each demonstrated superiority over traditional triplet regimens. Topics Covered1. MajesTEC-3Phase 3, open-label trial of teclistamab + daratumumab SC (n=291) vs. investigator's choice of DPd or DVd (n=296) in 587 patients with relapsed/refractory myeloma and 1–3 prior lines; prior BCMA-directed therapy and anti-CD38-refractory disease were exclusions (only 5% CD38-exposed, none were refractory). Initially presented at ASH 2025, with cytogenetic subgroup data updated at EHA 2026.Key results (34.5-month median follow-up):Median PFS not reached with Tec-Dara vs. 18.1 months with DPd/DVd; 36-month PFS 83.4% vs. 29.7% (HR 0.17)36-month OS 83.3% vs. 65.0% (HR 0.46)Severe infection rate front-loaded: ~35% → ~17% between the first and second 6-month windows, plateauing at ~10–11%/window beyond 12 months; overall grade 3–4 infection 54%, 4.6% fatal infections (mostly without IVIG prophylaxis)EHA 2026 cytogenetic subgroup: 2-year PFS 90% (0 HRCA), 82% (1 HRCA), 76% (≥2 HRCA) — vs. only 14% with DPd/DVd in patients with ≥2 HRCADiscussion points: Applicability to patients at 1st/2nd relapse seen in clinic today; whether infection risk limits use of Tec-Dara at first relapse; implications of the high-risk cytogenetic subgroup data.2. MajesTEC-9Phase 3 trial of teclistamab monotherapy vs. investigator's choice of PVd or Kd in relapsed/refractory myeloma enrolling a heavily anti-CD38-refractory population (100% CD38-exposed, 85% refractory) — the population MajesTEC-3 excluded. Natural comparator: CARTITUDE-4 (phase 3, cilta-cel vs. DPd/PVd in Len-refractory myeloma, 1–3 prior lines, ~25% CD38-refractory/exposed).Key results (~18-month median follow-up):18-month PFS 70% vs. 27% (HR 0.29); 18-month OS 79% vs. 69% (HR 0.6), despite ~2/3 of control-arm patients receiving BsAb/CAR T as subsequent therapyDiscussion points: Cross-trial comparison with CARTITUDE-4 — comparable 18-month PFS on cross-trial comparison, but differing populations (CARTITUDE-4 required Len-refractory disease; MajesTEC-9 enrolled a more CD38-refractory population) and differing maturity (~3-year vs. ~1.5-year follow-up); how Dr. Kapoor chooses between teclistamab and cilta-cel at earlier-line relapse in Len- and CD38-refractory patients, given the divergent toxicity profiles — ongoing infection risk with continuous BsAb dosing vs. the one-time cilta-cel infusion with its rare but potentially irreversible delayed neurotoxicity, IEC-enterocolitis, and CTTLN risk.3. MonumenTAL-3Phase 3 trial — the first phase 3 study of a GPRC5D-targeted bispecific — randomizing 864 patients with relapsed/refractory myeloma (mostly Len-refractory, ~10% CD38-exposed but none refractory) 1:1:1 to Tal-Dara-Pom (n=287), Tal-Dara (n=287), or DPd (n=290), each Talq arm compared against the common DPd control. Presented by Peter Voorhees at EHA 2026 and simultaneously published in NEJM.Key results (24.6-month median follow-up):Both Talq arms significantly improved PFS over DPd: Tal-DP HR 0.28, Tal-D HR 0.33 (both P<0.0001); 24-month PFS 81.3% (Tal-DP) and 77.6% (Tal-D) vs. ~51% (DPd)OS also favored both Talq arms, up to 89.2% vs. 79.1% (DPd) at 24 monthsSafety reflected regimen composition: more neutropenia/grade 3–4 infection with the Pom-containing arm; Talq arms showed frequent but mostly low-grade CRS, rare ICANS, and expected dysgeusia/skin-nail toxicity with weight loss (up to ~46% in Tal-DP)Discussion points: Not powered for a Tal-Dara vs. Tal-Dara-Pom comparison — did adding pomalidomide meaningfully change efficacy or safety; how to choose between a BCMA-directed and a GPRC5D-directed bispecific at first relapse given overlapping eligible populations with MajesTEC-3.4. LINKER-AL2 — AL AmyloidosisPhase 1/2, open-label study of single-agent,