Discussion
DLTs, MM, cytopenias, CRS, infections
EVENTS, CYTOPENIAS, INFECTIONS
MagnetisMM-1 is the first-in-human phase 1 study of elranatamab for patients with RRMM. The RP2D of 1,000 μg kgElranatamab demonstrated a manageable safety profile. DLTs were not observed during dose escalation, and a maximum tolerated dose was not reached. The most common TEAEs regardless of causality included CRS and cytopenias. With premedication and a single priming dose, the overall incidence of CRS was reduced to 66.7% and divided equally between grade 1 and grade 2, with no grade ≥3 events. Similarly, the overall incidence of ICANS was reduced to 13.3% and divided equally between grade 1 and grade 2, with no grade ≥3 events. Notably, subsequent studies with elranatamab implemented a step-up priming dose regimen (12 mg on day 1 and 32 mg on day 4) to further mitigate CRS and ICANS. In the present study, infections were common, and grade 3 and grade 4 events occurred in 21.8% and 5.5% of patients, respectively. These results highlight the importance of patient education, preventive measuresElranatamab showed predictable pharmacokinetics and low immunogenicity. Exposure increased in a dose-dependent manner and, consistent with maintenance or deepening of response after transition to less frequent (Q2W) dosing after ≥6 months of QW therapy, a dose of 1,000 µg kgImmunotherapeutic approaches, including both T-cell-engaging bispecific antibodies and CAR-T therapies, have provided important new opportunities for the treatment of patients with MM. Elranatamab represents a readily accessible off-the-shelf therapy with flexibility for biweekly dosing and provides an option for patients requiring immediate treatment or unable to access CAR-T therapies. Results from MagnetisMM-1 support the favorable risk–benefit profile of elranatamab and highlight a particularly compelling combination of attributes even among these emerging immunotherapiesThe interpretation of the results in this study is limited by its single-arm design and lack of direct comparison with other treatment options as well as by the small sample size in some subgroups. However, elranatamab induced durable clinical and molecular responses with predictable pharmacokinetics and a manageable safety profile for patients with RRMM. These results, along with emerging evidence for both PFS and OS, support the favorable risk–benefit profile of elranatamab at its RP2D (76 mg subcutaneously weekly) for patients with RRMM. Ongoing studies, including the pivotal phase 2 study (MagnetisMM-3), will further investigate elranatamab for patients with RRMM or newly diagnosed MM.