Sharma Poornima, Lin Xue, Xu Zhenzhen, Kanapuru Bindu, Theoret Marc R, Sokolic Robert, Fashoyin-Aje Lola A
Center for Biologics Evaluation and Research, Silver Spring, Maryland.
Center for Drug Evaluation and Research, Silver Spring, Maryland.
Clin Cancer Res. 2025 Aug 14;31(16):3362-3367. doi: 10.1158/1078-0432.CCR-24-4181.
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.
2024年4月4日，美国食品药品监督管理局（FDA）批准了idecabtagene vicleucel（ide-cel）用于接受过两种或更多线先前治疗（包括一种免疫调节剂、一种蛋白酶体抑制剂和一种抗CD38单克隆抗体）后复发或难治性多发性骨髓瘤的成人患者。批准基于KarMMa-3试验，这是一项针对386名患者的随机、开放标签试验。该研究将单次输注ide-cel与由研究者选择的五种抗骨髓瘤方案组成的标准治疗进行了比较。主要终点是无进展生存期，ide-cel组显著更长[风险比（HR）=0.49；95%置信区间（CI），0.38 - 0.64；P值<0.0001]。ide-cel组的中位无进展生存期为13.3个月（95%CI，11.8 - 16.1），标准治疗组为4.4个月（95%CI，3.4 - 5.9）。在222名接受ide-cel治疗的患者中，91%发生了细胞因子释放综合征（≥3级，5%），46%发生了神经毒性（≥3级，11%），39%发生了长期中性粒细胞减少，37%发生了长期血小板减少，9%发生了致命不良反应。首次和第二次中期总生存期分析结果显示，随机分组后约15个月内，ide-cel组的总生存期较差。鉴于ide-cel组早期死亡风险增加，FDA召开了肿瘤药物咨询委员会会议，讨论获益 - 风险考量。肿瘤药物咨询委员会以八比三投票认为，ide-cel对于拟用适应症的获益 - 风险是有利的。这是FDA首次批准针对该适应症的嵌合抗原受体T细胞疗法。
