Brexucabtagene autoleucel（brexu-cel）是一种自体抗CD19嵌合抗原受体（CAR）T细胞疗法，已在美国获得批准用于复发或难治性B细胞急性淋巴细胞白血病（B-ALL）成年患者以及在欧洲联盟获得批准用于≥26岁复发或难治性B-ALL患者。在ZUMA-3中进行了2年的随访，接受关键剂量的78例1期和2期R/R B-ALL患者的整体完全缓解（CR）率（CR + 完全血液恢复不完全的CR）为73％，中位总生存（OS）为25.4个月。报告了各种治疗前和随后的异基因干细胞移植（alloSCT）的结果。符合条件的成年患者罹患R/R B-ALL，并在经过调理化疗后接受了一次brexu-cel（1×10⁶ CAR T细胞/ kg）的输入。主要终点是经中央审查的CR / CRi比率。事后亚组分析是探索性的，在描述性统计方面提供了分析。纳入了1期和2期的患者（N=78），中位随访时间为29.7个月（范围20.7-58.3）。在所有已检查的前期治疗亚组中观察到了高CR / CRi率：1个前期疗程（87％，n=15）和≥2个前期疗程（70％，n=63）；有前期使用blinatumomab（63％，n=38）和没有使用blinatumomab（83％，n=40）；有前期使用inotuzumab（59％，n=17）和没有使用inotuzumab（77％，n=61）；以及有先前alloSCT（76％，n=29）和没有先前alloSCT（71％，n=49）。不同前期治疗亚组之间的≥3级细胞因子释放综合征、神经系统事件和与治疗相关的5级不良事件的发生率基本相似。在有（n=14）和没有（n=43）随后的alloSCT的回应者中，缓解期的中位数为44.2个月（95％CI，8.1至不可估计（NE））和18.6个月（95％CI，9.4至NE）；中位总生存（OS）分别为47.0个月（95％CI，10.2至NE）和未达到（95％CI，23.2至NE）。没有先前或随后的alloSCT的回应者（n=22）中，缓解期和OS均未达到中位数。在ZUMA-3中，不论之前的治疗和随后的alloSCT状况如何，R/R B-ALL的成年人都受益于brexu-cel，尽管在没有某些前期治疗且在早期治疗中，存活率似乎更好。需要进行其他研究来确定接受brexu-cel治疗的患者的前期治疗和后续alloSCT对结果的影响。 ©作者（或其雇主）2023年。在CC BY-NC下允许重复使用。不得进行商业再利用。由BMJ出版。

Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) are reported.Eligible adults had R/R B-ALL and received one infusion of brexu-cel (1×10⁶ CAR T cells/kg) following conditioning chemotherapy. The primary endpoint was the CR/CRi rate per central review. Post hoc subgroup analyses were exploratory with descriptive statistics provided.Phase 1 and 2 patients (N=78) were included with median follow-up of 29.7 months (range, 20.7-58.3). High CR/CRi rates were observed across all prior therapy subgroups examined: 1 prior line of therapy (87%, n=15) and ≥2 prior lines (70%, n=63); prior blinatumomab (63%, n=38) and no prior blinatumomab (83%, n=40); prior inotuzumab (59%, n=17) and no prior inotuzumab (77%, n=61); and prior alloSCT (76%, n=29) and no prior alloSCT (71%, n=49). The frequency of Grade ≥3 cytokine release syndrome, neurological events, and treatment-related Grade 5 adverse events were largely similar among prior therapy subgroups.Median duration of remission (DOR) in responders with (n=14) and without (n=43) subsequent alloSCT was 44.2 (95% CI, 8.1 to not estimable (NE)) and 18.6 months (95% CI, 9.4 to NE); median OS was 47.0 months (95% CI, 10.2 to NE) and not reached (95% CI, 23.2 to NE), respectively. Median DOR and OS were not reached in responders without prior or subsequent alloSCT (n=22).In ZUMA-3, adults with R/R B-ALL benefited from brexu-cel, regardless of prior therapies and subsequent alloSCT status, though survival appeared better in patients without certain prior therapies and in earlier lines of therapy. Additional studies are needed to determine the impact prior therapies and subsequent alloSCT have on outcomes of patients who receive brexu-cel.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.