Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial
Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial
复制标题
DOI：
10.1038/s41591-021-01622-0
复制
发表时间：
2021-12-17
期刊：
影响因子：
82.9
通讯作者：
Thieblemont, Catherine
中科院分区：
文献类型：
--
作者：
Fowler, Nathan Hale;Dickinson, Michael;Thieblemont, Catherine
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细胞淋巴瘤患者中具有临床意义的结果。在之前的一项针对r/r滤泡性淋巴瘤（FL）的tisagenlecleucel的初步研究中，71%的患者获得了完全缓解（CR）。在这里，我们报告了ELARA 2期多国试验的初步、预先指定的中期分析，该试验用于治疗两种或多种治疗线后患有r/r FL的成人或自体干细胞移植后复发的成人。NCT03568461)。主要终点为CR率（CRR）。次要终点包括总缓解率（ORR）、缓解持续时间、无进展生存期、总生存期、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治疗（中位随访时间16.59个月，四分位数范围13.8-20.21个月）。达到了主要终点。在疗效组（n = 94）中，CRR为69.1%(95%可信区间58.8 ~ 78.3)，ORR为86.2%（95%可信区间77.5 ~ 92.4）。在输液8周内，在安全组（n = 97）中，细胞因子释放综合征的发生率为48.5%(>级= 3,0%)，神经事件发生率为37.1%(>级= 3,3%)，免疫效应细胞相关神经毒性综合征（ICANS）发生率为4.1%(>级= 3,1%)，无治疗相关死亡。Tisagenlecleucel在广泛预处理的r/r FL（包括高危患者）中是安全有效的。在一项关键性2期试验的预先指定中期分析中，tisagenlecleucel，一种自体靶向cd19的CAR-T细胞疗法，在复发或难治性滤泡性淋巴瘤的成人患者中产生了高的完全缓解率和可控的安全性
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.In a prespecified interim analysis of a pivotal phase 2 trial, tisagenlecleucel, an autologous CD19-targeting CAR-T cell therapy, produced a high rate of complete responses with a manageable safety profile in adults with relapsed or refractory follicular lymphoma