On August 14, the U.S. Food and Drug Administration (FDA) granted accelerated approval to elranatamab-bcmm (Elrexfio), a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
MagnetisMM-3 Trial
Efficacy was evaluated in MagnetisMM-3 (ClinicalTrials.gov identifier NCT04649359), an open-label, single-arm, multicenter study that included patients with relapsed/refractory multiple myeloma. Patients had measurable disease by International Myeloma Working Group (IMWG) criteria at enrollment.
The main efficacy outcome measures were objective response rate, and duration of response, as assessed by a blinded independent central review based on IMWG criteria. The primary efficacy population consisted of 97 patients naive to prior BCMA-directed therapy who had previously received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The objective response rate in the 97 patients receiving the recommended dose was 57.7% (95% confidence interval [CI] = 47.3%–67.7%). With a median follow-up of 11.1 months among responders, the median duration of response was not reached (95% CI = 12 months to not reached). The duration of response rate at 6 months was 90.4% (95% CI = 78.4%–95.9%) and at 9 months was 82.3% (95% CI = 67.1%–90.9%).
The prescribing information for elranatamab has a Boxed Warning for life-threatening or fatal cytokine-release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity (ICANS). Among patients who received elranatamab at the recommended dose, cytokine-release syndrome occurred in 58% of patients, neurologic toxicity occurred in 59%, and ICANS occurred in 3.3%. Grade 3 cytokine-release syndrome occurred in 0.5% of patients, and grade 3 or 4 neurologic toxicity occurred in 7%. Because of the risks of cytokine-release syndrome and neurologic toxicity, including ICANS, elranatamab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the ELREXFIO REMS.
The most common adverse reactions (≥ 20%) in patients receiving the agent were cytokine-release syndrome, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common grade 3 or 4 laboratory abnormalities (≥ 20%) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.
The recommended elranatamab dosages include the following: “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, and 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. Elranatamab may be continued until disease progression or unacceptable toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.
This review also used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Priority Review, Breakthrough Therapy designation, and Orphan Drug designation.
