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. 2023 Nov 1;29(21):4331-4337. doi: 10.1158/1078-0432.CCR-23-0568.
In April 2022, the FDA approved axicabtagene ciloleucel (axi-cel) for adults with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. Approval was based on ZUMA-7, a randomized (1:1), open-label trial in 359 patients with primary refractory LBCL (74%) or early relapse who were transplant candidates. The study compared a single course of axi-cel to standard therapy, consisting of chemoimmunotherapy followed by high-dose therapy and autologous hematopoietic stem cell transplantation (HSCT) in responding patients. Overall, 94% of the experimental arm received chimeric antigen receptor (CAR) T-cell product, and 35% of the control arm received on-protocol HSCT. The primary endpoint was event-free survival, which was significantly longer in the axi-cel arm with an HR of 0.40 (95% confidence interval, 0.31-0.51; P value < 0.0001) and estimated median of 8.3 months, versus 2.0 months with standard therapy. Among 168 recipients of axi-cel, cytokine release syndrome occurred in 92% (Grade ≥ 3, 7%), neurologic toxicity in 74% (Grade ≥ 3, 25%), prolonged cytopenias in 33%, and fatal adverse reactions in 1.8%. This is the first FDA approval of a CAR T-cell therapy for LBCL in the second-line setting and reflects a potential paradigm shift.
2022 年 4 月，FDA 批准 axicabtagene ciloleucel（axi-cel）用于一线化疗免疫治疗耐药或一线化疗免疫治疗后 12 个月内复发的成人弥漫性大 B 细胞淋巴瘤（LBCL）。该批准基于 ZUMA-7 试验，这是一项在 359 例原发性难治性 LBCL（74%）或早期复发且为移植候选者的患者中进行的随机（1:1）、开放标签试验。该研究比较了 axi-cel 单药治疗与标准治疗（包括化疗免疫治疗，然后在有应答的患者中进行大剂量治疗和自体造血干细胞移植（HSCT））。总体而言，实验臂 94%的患者接受了嵌合抗原受体（CAR）T 细胞产品，对照臂 35%的患者接受了方案规定的 HSCT。主要终点是无事件生存，axi-cel 臂的无事件生存显著更长，风险比为 0.40（95%置信区间，0.31-0.51；P 值<0.0001），估计中位无事件生存时间为 8.3 个月，而标准治疗组为 2.0 个月。在 168 例接受 axi-cel 的患者中，细胞因子释放综合征发生率为 92%（≥3 级，7%），神经毒性发生率为 74%（≥3 级，25%），持续性血细胞减少发生率为 33%，致命不良反应发生率为 1.8%。这是 FDA 首次批准 CAR T 细胞疗法用于二线弥漫性大 B 细胞淋巴瘤，反映了潜在的范式转变。
