Elranatamab: Mechanism of Action, Clinical, and Translational Science

Elranatamab (ELREXFIO) is a humanized bispecific antibody approved for patients with relapsed/refractory multiple myeloma (RRMM). Elranatamab engages CD3 on T cells and B-cell maturation antigen (BCMA) on myeloma cells to induce T cell-mediated myeloma cell cytolysis. The recommended subcutaneous elranatamab dosing consists of fixed step-up doses of 12 mg on day 1 and 32 mg on day 4 to mitigate the incidence and severity of cytokine release syndrome (CRS), followed by the full fixed dose of 76 mg once weekly (QW) from weeks 2 to 24. In responders, 76 mg QW is reduced to every 2 weeks (Q2W) after ≥ 6 QW cycles and to every 4 weeks after ≥ 6 Q2W cycles. The full dose (76 mg QW) results in a higher probability of achieving an objective response versus lower doses without worsening the safety profile. This regimen was based on the collective safety, efficacy, pharmacokinetic, and pharmacodynamic data from MagnetisMM-1, -2, -3, and -9. In the pivotal MagnetisMM-3 study, in patients with BCMA-naive RRMM, elranatamab resulted in a 61.0% overall response rate; 37.4% achieved complete response or stringent complete response. Median duration of response was not yet reached; the probability of maintaining response at 30 months was 61.0%. Median progression-free and overall survival were 17.2 and 24.6 months, respectively. In MagnetisMM-3 patients, common adverse events (≥ 40%; any grade/grade 3/4) included infections (71.7%/38.5%), CRS (58.8%/0.5%), anemia (53.5%/42.2%), neutropenia (46.0%/44.4%), and diarrhea (42.8%/3.2%). Elranatamab demonstrated deep and durable responses, a manageable safety profile, and low-grade CRS with predictable timing. Elranatamab is being further evaluated as monotherapy or combination therapy in earlier treatment lines.