On August 14, 2023, the FDA accelerated the approval of elranatamab-bcmm (Elrexfio; Pfizer), a bispecific B-cell maturation antigen (BCMA)–directed CD3 T-cell engager, for the treatment of adults with relapsed or refractory multiple myeloma who have received at least 4 previous lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
The FDA granted this approval priority review and breakthrough and orphan drug designations.
The approval was based on results from cohort A of the MagnetisMM-3 study, an open-label, single-arm, multicenter, phase 2 clinical trial assessing elranatamab monotherapy in 123 patients with relapsed or refractory multiple myeloma whose disease was refractory to at least 1 PI, 1 immunomodulatory drug, and 1 anti-CD38 antibody. At the time of enrollment, patients had measurable disease by International Myeloma Working Group (IMWG) criteria.
The main efficacy measures were objective response rate (ORR) and duration of response (DOR), as assessed by a blinded independent central review based on IMWG criteria. Of the 123 patients enrolled in the study, 97 had not received previous BCMA-directed therapy and had received at least 4 previous lines of therapy, including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
The ORR in those 97 patients was 57.7% (95% confidence interval [CI], 47.3-67.7). At 6 months, the DOR was 90.4% (95% CI, 78.4-95.9), and at 9 months it was 82.3% (95% CI, 67.1-90.9). At a median follow-up of 11.1 months, the median DOR was not reached (95% CI, 12 months-not reached).
The most common (≥20%) adverse reactions were cytokine release syndrome (CRS), fatigue, injection-site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common (≥20%) grade 3 or 4 laboratory abnormalities were decreased levels of lymphocytes, neutrophils, hemoglobin, white blood cells, and platelets.
The prescribing information for elranatamab includes a boxed warning regarding the risk for life-threatening or fatal CRS and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS). Among patients treated with elranatamab at the recommended dose, 58% had CRS (including 0.5%, grade 3), 59% had neurologic toxicity (including 7%, grade 3/4), and 3.3% had ICANS.
Because of the risks for CRS and neurologic toxicity, including ICANS, elranatamab is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS) program called ELREXFIO REMS.
To reduce the risk for CRS, the recommended dosing for elranatamab includes the following step-up dosing: step-up dose 1 of 12 mg on day 1, step-up dose 2 of 32 mg on day 4, followed by the first treatment dose of 76 mg on day 8, then 76 mg weekly thereafter through week 24. For patients who have received at least 24 weeks of elranatamab and have achieved partial responses or better and maintained responses for at least 2 months, the dose interval should transition to an every-2-week schedule. Treatment with elranatamab may be continued until disease progression or unacceptable toxicity. Patients should be hospitalized for 48 hours after administration of the first step-up dose, and for 24 hours after administration of the second step-up dose.
