FDA Approval Summary: Idecabtagene Vicleucel for the Treatment of Triple-Class-Exposed, Relapsed or Refractory Multiple Myeloma.

On April 4, 2024, the FDA approved idecabtagene vicleucel (ide-cel) for adults with relapsed or refractory multiple myeloma after two or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Approval was based on KarMMa-3, a randomized, open-label trial in 386 patients. The study compared a single infusion of ide-cel to standard-of-care treatment consisting of the investigator's choice of five anti-myeloma regimens. The primary endpoint was progression-free survival, which was significantly longer in the ide-cel arm [HR = 0.49; 95% confidence interval (CI), 0.38-0.64; P value <0.0001]. The median progression-free survival was 13.3 months (95% CI, 11.8-16.1) in the ide-cel arm and 4.4 months (95% CI, 3.4-5.9) in the standard-of-care arm. Among the 222 recipients of ide-cel, cytokine release syndrome occurred in 91% (grade ≥3, 5%), neurologic toxicity in 46% (grade ≥3, 11%), prolonged neutropenia in 39%, prolonged thrombocytopenia in 37%, and fatal adverse reactions in 9%. Results from the first and second interim overall survival analyses demonstrated overall survival detriment in the ide-cel arm for approximately 15 months after randomization. Given the increased risk of early deaths in the ide-cel arm, the FDA convened an Oncologic Drugs Advisory Committee meeting to discuss the benefit-risk considerations. The Oncologic Drugs Advisory Committee voted eight to three that the benefit-risk for ide-cel was favorable for the proposed indication. This is the first FDA approval of a chimeric antigen receptor T-cell therapy for this indication.