On August 14, 2023, the FDA accelerated the approval of elranatamab-bcmm (Elrexfio; Pfizer) for the treatment of adults with relapsed or refractory multiple myeloma (MM) who have received ≥4 lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
The FDA granted elranatamab priority review and breakthrough and orphan drug designations.
Elranatamab is a subcutaneous bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, an immunotherapy that activates T cells to kill myeloma cells.
The FDA approval was based on the results of cohort A of the phase 2 MagnetisMM-3 study (NCT04649359), an open-label, single-arm, multicenter clinical trial of 123 patients with relapsed or refractory MM whose disease is refractory to at least 1 PI, 1 immunomodulatory drug, and 1 anti-CD38 antibody. At study enrollment, all 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 enrolled patients, 97 patients had not received BCMA-directed therapy and had received ≥4 lines of therapy, including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
Among those 97 patients, the ORR to elranatamab was 57.7% (95% confidence interval [CI], 47.3-67.7). The median time to first response was 1.2 months. The DOR rates were 90.4% (95% CI, 78.4-95.9) at 6 months and 82.3% (95% CI, 67.1-90.9) at 9 months. At a median follow-up of 11.1 months, the median DOR was not reached (95% CI, 12 months-not reached).
“Most multiple myeloma patients will experience relapse or resistance of their disease to treatment, often facing increased symptom burden and lowering their chance of surviving longer with each attempted line of therapy,” Ajay Nooka, MD, MPH, Director of the Myeloma Program in the Department of Hematology and Medical Oncology at Emory University School of Medicine, Atlanta, GA, and investigator in the MagnetisMM clinical trial, said in a press release. “By offering durable clinical response with an established safety profile and the convenience of subcutaneous administration, Elrexfio provides a much-needed new option for heavily pre-treated MM patients who are struggling with relapsed myeloma,” Dr Nooka added.
The most common (≥20%) adverse reactions 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, 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 of elranatamab includes a boxed warning regarding the risk for life-threatening or fatal CRS and neurologic toxicity, including immune effector cell–associated neurotoxicity (ICANS). Among patients who received elranatamab at the recommended dose, 58% had CRS (including 0.5% grade 3), 59% had neurologic toxicity (including 7% grade 3 or 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 step-up dosing of 12 mg on day 1, 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 ≥24 weeks of elranatamab treatment and have achieved partial responses or better and maintained responses for ≥2 months, the dose interval should transition to an every-2-week schedule. Elranatamab therapy may be continued until disease progression or unacceptable adverse events.
Patients should be hospitalized for 48 hours after the administration of the first step-up dose and for 24 hours after the administration of the second step-up dose.
Continued approval for this indication is contingent on the verification of clinical benefit in a confirmatory trial or trials. According to the manufacturer, the MagnetisMM-5 study will serve as a confirmatory trial to support the clinical benefit of elranatamab.