FDA Approval Summary: Idecabtagene Vicleucel for the Treatment of Triple-Class–Exposed, Relapsed or Refractory Multiple Myeloma
Poornima Sharma, Xue Lin, Zhenzhen Xu, Bindu Kanapuru, Marc R. Theoret, Robert Sokolic, Lola A. Fashoyin‐Aje
Abstract
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.