FDA Grants Accelerated Approval to Elrexfio for Relapsed/Refractory Multiple Myeloma

The Food and Drug Administration (FDA) has granted accelerated approval to Elrexfio^™ (elranatamab-bcmm) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Elranatamab is a B-cell maturation antigen (BCMA)-CD3-directed bispecific antibody that binds to BCMA on multiple myeloma cells and CD3 on T-cells leading to cytolysis of the BCMA-expressing cells. The accelerated approval was based on response rate and durability of response observed in the open-label, single-arm phase 2 MagnetisMM-3 study (ClinicalTrials.gov Identifier: NCT04649359).

The study enrolled patients who were refractory to at least 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 anti-CD38 monoclonal antibody; 123 participants were naïve to prior BCMA-directed therapy (Cohort A), while 64 had prior BCMA-directed antibody drug conjugate or chimeric antigen receptor (CAR) T-cell therapy (Cohort B). The efficacy population included 97 patients who were not exposed to prior BCMA-directed therapy and received at least 4 prior lines of treatment.

Among these 97 BCMA-directed therapy naïve patients, the objective response rate (ORR) was 57.7% (95% CI, 47.3-67.7), with 25.8% of patients having a stringent complete response or a complete response, 25.8% having a very good partial response, and 6.2% having a partial response. Median time to first response was 1.22 months (range, 0.9-6.5). Median duration of response (DOR) was not reached (95%CI, 12.0, not estimable). With a median follow-up of 11.1 months (95% CI, 10.6-12.0) among responders, 90.4% (95% CI, 78.4-95.9) maintained the response for at least 6 months and 82.3% (95% CI, 67.1-90.9) maintained the response for at least 9 months.

Among the 63 patients in Cohort B who had received at least 4 prior lines of therapy, the confirmed ORR was 33.3% (95% CI, 22.0-46.3) and median DOR was not reached (95% CI, not estimable, not estimable) after a median follow-up of 10.2 months; DOR rate at 9 months was 84.3% (95% CI, 58.7-94.7).

The most common adverse reactions reported in the study were cytokine release syndrome (CRS), fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, pyrexia, decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.

The prescribing information for Elrexfio includes a Boxed Warning regarding the risks of CRS and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome. Because of these risks, Elrexfio is only available through a restricted program called the Elrexfio Risk Evaluation and Mitigation Strategy (REMS). To reduce the incidence and severity of CRS, Elrexfio should be administered according to the step-up dosing schedule described in the labeling. 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.

Elrexfio is supplied as a ready-to-use solution in 76mg/1.9 mL (40mg/mL) and 44mg/1.1 mL (40mg/mL) single-dose vials. The solution does not require dilution prior to subcutaneous administration. The product is expected to be available in the coming weeks. Pfizer announced that the MagnetisMM-5 study (ClinicalTrials.gov Identifier: NCT05020236) will serve as the confirmatory trial to support the clinical benefit of Elrexfio.