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

On April 4, 2024, the Food and Drug Administration (FDA) approved idecabtagene vicleucel (ide-cel) for adults with relapsed or refractory multiple myeloma (RRMM) after two or more prior lines of therapy, including an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), 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 (SOC) treatment consisting of the investigator's choice of five anti-myeloma regimens. The primary endpoint was progression-free survival (PFS), 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 PFS 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 SOC arm. Among the 222 recipients of ide-cel, cytokine release syndrome (CRS) 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 (OS) analyses demonstrated OS detriment in the ide-cel arm for approximately 15 months after randomization. Given the increased risk of early deaths in the ide-cel arm, FDA convened an Oncologic Drugs Advisory Committee (ODAC) meeting to discuss the benefit-risk considerations. ODAC voted 8 to 3 that the benefit-risk for ide-cel was favorable for the proposed indication. This is the first FDA approval of a chimeric antigen receptor (CAR) T-cell therapy for this indication.