美国德克萨斯大学MD安德森癌症中心Sattva S. Neelapu研究团队近期取得重要研究进展。他们研究发现Axicabtagene cilolucel(axis -cel)作为高危大B细胞淋巴瘤的一线治疗方案的一部分是安全有效的。相关论文于2022年3月21日发表在《自然—医学》杂志上。

在第2期、多中心、单臂ZUMA-12研究 (ClinicalTrials.gov NCT03761056) 中，研究人员评估了axicabtagene ciloleucel (axi-cel)，一种自体抗CD19嵌合抗原受体 (CAR) T细胞疗法，作为40名高危LBCL患者的一线治疗方案的一部分。该项试验已完成了应征工作。主要预后指标是完全缓解率（CRR）。次要预后指标为客观缓解率(ORR)、缓解时间(DOR)、无事件生存期(EFS)、无进展生存期(PFS)、总生存期(OS)、安全性评估、中枢神经系统(CNS)复发和血液中CAR-T细胞和细胞因子水平。

疗效可评估患者(n=37)的主要预后指标达到78%的CRR(95%可信区间(CI)， 62-90)和89%的ORR (95% CI, 75-97)。截至2021年5月17日（中位随访时间为15.9个月），73%的患者保持客观缓解，未达到中位 DOR、EFS 和 PFS。患者发生细胞因子释放综合征(CRS，≥3级) 3例(8%)，发生神经系统事件9例(23%)。没有与治疗相关的 5级事件发生。所有患者均出现强劲的CAR T细胞扩增，达到峰值的中位时间为8天。研究人员得出结论，axis-cel作为高危LBCL一线治疗方案的一部分是非常有效的，并且具有可控的安全性。

据介绍，高危大B细胞淋巴瘤(LBCL)使用标准一线免疫疗法的效果较差。

附：英文原文

Title: Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial

Author: Neelapu, Sattva S., Dickinson, Michael, Munoz, Javier, Ulrickson, Matthew L., Thieblemont, Catherine, Oluwole, Olalekan O., Herrera, Alex F., Ujjani, Chaitra S., Lin, Yi, Riedell, Peter A., Kekre, Natasha, de Vos, Sven, Lui, Christine, Milletti, Francesca, Dong, Jinghui, Xu, Hairong, Chavez, Julio C.

Issue&Volume: 2022-03-21

Abstract: High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR Tcells and cytokines. The primary endpoint in efficacy-evaluable patients (n=37) was met, with 78% CRR (95% confidence interval (CI), 62–90) and 89% ORR (95% CI, 75–97). As of 17May 2021 (median follow-up, 15.9months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile.

DOI: 10.1038/s41591-022-01731-4

Source: https://www.nature.com/articles/s41591-022-01731-4