Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor-T cell therapy with clinically meaningful outcomes demonstrated in patients with relapsed/refractory (r/r) B-cell lymphoma. In a previous pilot study of tisagenlecleucel in r/r follicular lymphoma (FL), 71% of patients achieved a complete response (CR). Here we report the primary, prespecified interim analysis of the ELARA phase 2 multinational trial of tisagenlecleucel in adults with r/r FL after two or more treatment lines or who relapsed after autologous stem cell transplant (no. NCT03568461). The primary endpoint was CR rate (CRR). Secondary endpoints included overall response rate (ORR), duration of response, progression-free survival, overall survival, pharmacokinetics and safety. As of 29 March 2021, 97/98 enrolled patients received tisagenlecleucel (median follow-up, 16.59 months; interquartile range, 13.8–20.21). The primary endpoint was met. In the efficacy set (n = 94), CRR was 69.1% (95% confidence interval, 58.8–78.3) and ORR 86.2% (95% confidence interval, 77.5–92.4). Within 8 weeks of infusion, rates of cytokine release syndrome were 48.5% (grade ≥3, 0%), neurological events 37.1% (grade ≥3, 3%) and immune effector cell-associated neurotoxicity syndrome (ICANS) 4.1% (grade ≥3, 1%) in the safety set (n = 97), with no treatment-related deaths. Tisagenlecleucel is safe and effective in extensively pretreated r/r FL, including in high-risk patients.

Tisagenlecleucel 是一种自体抗 CD19 嵌合抗原受体 T 细胞疗法，在复发/难治性 (r/r) B 细胞淋巴瘤患者中显示出具有临床意义的结果。在之前的 tisagenlecleucel 治疗 r/r 滤泡性淋巴瘤 (FL) 的试点研究中，71% 的患者达到完全缓解 (CR)。在此，我们报告了 ELARA 2 期多国试验的主要、预先指定的中期分析，该试验针对 tisagenlecleucel 成人，在接受两种或多种治疗后患有复发/难治性 FL 或在自体干细胞移植后复发的成人中（编号 NCT03568461）。主要终点是 CR 率 (CRR)。次要终点包括总体缓解率（ORR）、缓解持续时间、无进展生存期、总体生存期、药代动力学和安全性。截至 2021 年 3 月 29 日，97/98 名入组患者接受了 tisagenlecleucel（中位随访时间为 16.59 个月；四分位数范围为 13.8–20.21）。达到了主要终点。在疗效组中 ( n = 94)，CRR 为 69.1%（95% 置信区间，58.8–78.3），ORR 为 86.2%（95% 置信区间，77.5–92.4）。输注8周内，细胞因子释放综合征发生率为48.5%（≥3级，0%），神经系统事件发生率为37.1%（≥3级，3%），免疫效应细胞相关神经毒性综合征（ICANS）为4.1%（等级≥3%）。 ≥3, 1%) 在安全组 ( n = 97) 中，没有与治疗相关的死亡。 Tisagenlecleucel 对于广泛预处理的 r/r FL（包括高危患者）是安全有效的。