Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Clin Cancer Res. 2024 Jul 15;30(14):2865-2871. doi: 10.1158/1078-0432.CCR-24-0378.
In February 2022, the FDA approved ciltacabtagene autoleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting the B-cell maturation antigen, for adult patients with relapsed/refractory multiple myeloma after ≥4 lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Approval was based on overall response rate (ORR), complete response (CR) rate, and duration of response (DoR) in 97 adult patients in a single-arm, open-label, multicenter phase 2 trial (CARTITUDE-1 [NCT03548207]). Patients received a single infusion of ciltacabtagene autoleucel, preceded by lymphodepleting chemotherapy. Of the 97 patients evaluable, ORR was 97.9% [95% confidence interval (CI), 92.7-99.7] with a stringent CR rate of 78.4% (95% CI, 68.8-86.1). After median follow-up of 18 months, the median DoR was 21.8 months (95% CI, 21.8-not estimable [NE]) in responders (PR or better) and NE (95% CI, 21.8 months-NE) in patients who achieved stringent CR. Serious adverse reactions occurred in 55% of the 97 patients evaluated for safety. Grade 3 or higher cytokine release syndrome (CRS) and neurologic toxicities occurred in 5% and 11% of the patients, respectively, leading to a Risk Evaluation and Mitigation Strategy. Neurologic toxicities included immune effector cell-associated neurologic syndrome, typically seen with CAR-T products, parkinsonism, peripheral neuropathy, cranial nerve palsies, and Guillain-Barré syndrome. One fatal case of hemophagocytic lymphohistiocytosis/macrophage activation syndrome occurred. Prolonged and recurrent grade 3 or 4 cytopenias occurred; a single patient required hematopoietic stem-cell rescue.
2022 年 2 月，美国食品药品监督管理局（FDA）批准 cilta-cabtagene autoleucel，一种针对 B 细胞成熟抗原的嵌合抗原受体（CAR）T 细胞疗法，用于治疗≥4 线治疗（包括免疫调节剂、蛋白酶体抑制剂和抗 CD38 单克隆抗体）后复发/难治性多发性骨髓瘤的成年患者。批准基于 97 例成年患者的单臂、开放标签、多中心 2 期试验（CARTITUDE-1[NCT03548207]）中的总体缓解率（ORR）、完全缓解（CR）率和缓解持续时间（DoR）。患者接受单次 cilta-cabtagene autoleucel 输注，输注前进行淋巴细胞耗竭化疗。在 97 例可评估患者中，ORR 为 97.9%[95%置信区间（CI），92.7-99.7]，严格 CR 率为 78.4%（95%CI，68.8-86.1）。在中位随访 18 个月后，缓解者（PR 或更好）的中位 DoR 为 21.8 个月（95%CI，21.8-NE），严格 CR 者的 NE（95%CI，21.8 个月-NE）。在接受安全性评估的 97 例患者中，有 55%发生严重不良反应。分别有 5%和 11%的患者发生 3 级或更高级别的细胞因子释放综合征（CRS）和神经毒性，导致风险评估和缓解策略的实施。神经毒性包括免疫效应细胞相关神经综合征，这是 CAR-T 产品的常见现象，包括帕金森病、周围神经病、颅神经麻痹和格林-巴利综合征。发生了 1 例噬血细胞性淋巴组织细胞增多症/巨噬细胞活化综合征致死病例。持续性和复发性 3 级或 4 级血细胞减少症；1 例患者需要造血干细胞挽救。
