Background
Phase 2, open-label, single-arm trial (MagnetisMM-3, Cohort A). N=123 BCMA-naïve patients with relapsed or refractory multiple myeloma after ≥3 prior lines including a PI, IMiD, and anti-CD38 antibody (triple-class refractory), refractory to last treatment. Elranatamab is an off-the-shelf BCMAxCD3 bispecific antibody (Pfizer).
Interventions and follow up
Regimen: Elranatamab SC step-up 12 → 32 mg, then 76 mg SC weekly (switched to q2wk after cycle 6 in responders)
Population: BCMA-naïve, triple-class–exposed R/R MM
Primary endpoint: Confirmed objective response rate (ORR) by blinded independent central review
mFollow up: 14.7 months
Population: BCMA-naïve, triple-class–exposed R/R MM
Primary endpoint: Confirmed objective response rate (ORR) by blinded independent central review
mFollow up: 14.7 months
Results
ORR: 61.0% (95% CI 51.6–69.7%)
≥CR rate: 35.0%
mDOR: Not reached
mPFS: Not reached
15-mo rates: DOR 71.5%; PFS 50.9%; OS 56.7%
≥CR rate: 35.0%
mDOR: Not reached
mPFS: Not reached
15-mo rates: DOR 71.5%; PFS 50.9%; OS 56.7%
Adverse events
CRS: Any grade 57.7% (all grade 1–2), grade ≥3 0%
Infections: Any grade 69.9%, grade ≥3 39.8%
Hematologic (grade ≥3): Neutropenia 48.8%, anemia 37.4%; biweekly switch reduced grade ≥3 AEs from 58.6% to 46.6%
Infections: Any grade 69.9%, grade ≥3 39.8%
Hematologic (grade ≥3): Neutropenia 48.8%, anemia 37.4%; biweekly switch reduced grade ≥3 AEs from 58.6% to 46.6%
Conclusions
Elranatamab achieved a 61% ORR with 35% ≥CR and durable responses (DOR/PFS/OS medians not reached at 14.7 months) in BCMA-naïve RRMM, with all CRS events grade 1–2 and no grade ≥3 CRS, confirming BCMAxCD3 bispecific antibodies as a highly active class.
Key Limitations
Single-arm design without a randomized comparator. Substantial grade ≥3 infection rate (39.8%) reflects on-target hypogammaglobulinemia, mandating IVIG and antimicrobial prophylaxis. Cohort A excluded prior BCMA-directed therapy, limiting generalizability to BCMA-exposed patients (addressed in Cohort B). Continuous dosing imposes ongoing treatment burden despite the biweekly de-escalation.
Clinical Context
FDA granted accelerated approval to elranatamab (Elrexfio) in August 2023 for RRMM after ≥4 prior lines; EMA approval followed. It is the second BCMAxCD3 bispecific approved for myeloma after teclistamab, with a convenient weekly-to-biweekly SC schedule. Infection prophylaxis and IVIG are standard. ESMO-MCBS reflects meaningful benefit.