MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response
Elranatamab produced responses in 61% of heavily pretreated myeloma patients and showed that dosing can be thinned to every two weeks once patients respond.
MagnetisMM-3 was a phase 2 single-arm study of elranatamab, a subcutaneous BCMA x CD3 bispecific, in 123 patients with triple-class-exposed relapsed or refractory multiple myeloma who had not received prior BCMA-directed therapy (cohort A). After two step-up doses and weekly dosing, patients who had responded for at least six months moved to every-two-week dosing. The overall response rate was 61% with complete response or better in 35%; most responses were ongoing at a year. CRS occurred in about 58% of patients, all grade 1-2 with the priming regimen, and neurotoxicity in a small minority. Infections were the main serious toxicity. The FDA granted accelerated approval in 2023.
- 123 BCMA-naive, triple-class-exposed patients (cohort A); median 5 prior lines.
- Overall response 61%; complete response or better 35%.
- Responses were durable, with most responders still in response at 12 months.
- CRS in about 58%, all grade 1-2 after two step-up doses; ICANS uncommon.
- Responders switched to every-two-week dosing after 6 months without loss of response in most cases.
Elranatamab confirmed that BCMA bispecifics are a class, not a one-off, and its protocol-built dose reduction after response set a precedent for lowering the immunosuppressive burden of T-cell engagers. Patients now have two approved BCMA bispecifics and one against GPRC5D (talquetamab). Choosing between them, and sequencing them with CAR-T, remains guided by availability and toxicity profile rather than head-to-head data.
- Single-arm; no comparator or randomised evidence at approval.
- Excluded patients with prior BCMA therapy in the registrational cohort; cohort B (BCMA-exposed) had lower responses.
- Infection risk and hypogammaglobulinaemia similar to teclistamab.
- Durability beyond two years still being reported.