On March 26, the U.S. Food and Drug Administration (FDA) approved idecabtagene vicleucel (Abecma) for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. This is the first FDA-approved cell-based gene therapy for multiple myeloma.
Idecabtagene vicleucel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose is customized using a patient’s own T cells, which are collected, genetically modified, and infused back into the patient.
Safety and efficacy were evaluated in the phase II KarMMa trial, a multicenter study of 127 patients with relapsed and refractory multiple myeloma who received at least three prior lines of antimyeloma therapies. Eighty-eight percent of patients had received four or more prior lines of therapies. Efficacy was evaluated in 100 patients who received idecabtagene vicleucel in the dose range of 300 to 460 x 106 CAR-positive T cells. Efficacy was established based on overall response rate, complete response rate, and duration of response as evaluated by an Independent Response committee using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma.
The overall response rate was 72% (95% confidence interval [CI] = 62%–81%) and the complete response rate was 28% (95% CI = 19%–38%). An estimated 65% of patients who achieved complete response maintained that response for at least 12 months.
The idecabtagene vicleucel label carries a boxed warning for cytokine-release syndrome, neurologic toxicities, hemophagocytic lymphohistiocytosis/ macrophage activation syndrome, and prolonged cytopenias. The most common side effects of idecabtagene vicleucel include cytokine-release syndrome, infections, fatigue, musculoskeletal pain, and hypogammaglobulinemia.
Idecabtagene vicleucel is approved with a risk evaluation and mitigation strategy requiring that health-care facilities that dispense the therapy must be specially certified to recognize and manage cytokine-release syndrome and nervous system toxicities. To evaluate long-term safety, the FDA is requiring the manufacturer to conduct a post-marketing observational study involving patients treated with idecabtagene vicleucel.
The recommended dose range for idecabtagene vicleucel is 300 to 460 × 106 CAR-positive T cells.