Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Oncologist. 2022 Jul 5;27(7):587-594. doi: 10.1093/oncolo/oyac054.
In March 2021, the U.S. Food and Drug Administration granted accelerated approval to axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor T-cell therapy, for the treatment of adult patients with relapsed or refractory follicular lymphoma (r/r FL) after at least 2 lines of systemic therapy. Approval was based on ZUMA-5, a single-arm, open-label, multicenter trial that evaluated a single infusion of axicabtagene ciloleucel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine, in this population. Efficacy was based on objective response rate (ORR) and duration of response (DOR) as determined by an independent review committee. Among 81 patients in the primary efficacy analysis, having a median of 3 (range 2-9) prior lines of systemic therapy, the ORR was 91% (95% confidence interval [CI]: 83-96) with a complete remission (CR) rate of 60% and a median time-to-response of 1 month. The median DOR was not reached, and the 1-year rate of continued remission was 76% (95% CI: 64-85). For all leukapheresed patients with FL in this trial (n = 123), the ORR was 89% (95% CI: 83-94) with a CR rate of 62%. Among 146 patients with indolent lymphoma evaluated for safety, cytokine release syndrome occurred in 84% (Grade ≥3, 8%) and neurological toxicities occurred in 77% (Grade ≥3, 21%), leading to implementation of a risk evaluation and mitigation strategy. Serious adverse reactions occurred in 48%. Post-marketing studies will further evaluate clinical benefit in patients with r/r FL and long-term safety.
2021 年 3 月，美国食品和药物管理局批准 axicabtagene ciloleucel（一种 CD19 导向的嵌合抗原受体 T 细胞疗法）用于治疗至少接受 2 线系统治疗后复发或难治性滤泡淋巴瘤（r/r FL）的成年患者。批准基于 ZUMA-5 试验，这是一项单臂、开放标签、多中心试验，评估了在该人群中单次输注 axicabtagene ciloleucel 前，先用环磷酰胺和氟达拉滨进行淋巴清除化疗。疗效基于独立审查委员会确定的客观缓解率（ORR）和缓解持续时间（DOR）。在主要疗效分析的 81 例患者中，中位接受了 3 线（范围 2-9 线）以前的系统治疗，ORR 为 91%（95%CI：83-96），完全缓解（CR）率为 60%，中位反应时间为 1 个月。中位 DOR 尚未达到，1 年持续缓解率为 76%（95%CI：64-85）。在这项试验中，所有滤泡淋巴瘤患者（n=123）的 ORR 为 89%（95%CI：83-94），CR 率为 62%。在 146 例评估安全性的惰性淋巴瘤患者中，细胞因子释放综合征发生率为 84%（≥3 级，8%），神经毒性发生率为 77%（≥3 级，21%），导致实施风险评估和缓解策略。48%的患者发生严重不良反应。上市后研究将进一步评估 r/r FL 患者的临床获益和长期安全性。
