Mayo Clinic, Rochester, MN.
The University of Texas MD Anderson Cancer Center, Houston, TX.
J Clin Oncol. 2023 May 10;41(14):2594-2606. doi: 10.1200/JCO.22.01797. Epub 2023 Feb 8.
Brexucabtagene autoleucel (brexu-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory mantle cell lymphoma (MCL). This therapy was approved on the basis of the single-arm phase II ZUMA-2 trial, which showed best overall and complete response rates of 91% and 68%, respectively. We report clinical outcomes with brexu-cel in the standard-of-care setting for the approved indication.
Patients who underwent leukapheresis between August 1, 2020 and December 31, 2021, at 16 US institutions, with an intent to manufacture commercial brexu-cel for relapsed/refractory MCL, were included. Patient data were collected for analyses of responses, outcomes, and toxicities as per standard guidelines.
Of 189 patients who underwent leukapheresis, 168 (89%) received brexu-cel infusion. Of leukapheresed patients, 79% would not have met ZUMA-2 eligibility criteria. Best overall and complete response rates were 90% and 82%, respectively. At a median follow-up of 14.3 months after infusion, the estimates for 6- and 12-month progression-free survival (PFS) were 69% (95% CI, 61 to 75) and 59% (95% CI, 51 to 66), respectively. The nonrelapse mortality was 9.1% at 1 year, primarily because of infections. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 8% and 32%, respectively. In univariable analysis, high-risk simplified MCL international prognostic index, high Ki-67, aberration, complex karyotype, and blastoid/pleomorphic variant were associated with shorter PFS after brexu-cel infusion. Patients with recent bendamustine exposure (within 24 months before leukapheresis) had shorter PFS and overall survival after leukapheresis in intention-to-treat univariable analysis.
In the standard-of-care setting, the efficacy and toxicity of brexu-cel were consistent with those reported in the ZUMA-2 trial. Tumor-intrinsic features of MCL, and possibly recent bendamustine exposure, may be associated with inferior efficacy outcomes.
Brexucabtagene autoleucel（brexu-cel）是一种自体 CD19 导向的嵌合抗原受体（CAR）T 细胞疗法，已获批用于复发/难治性套细胞淋巴瘤（MCL）。该疗法是基于单臂 II 期 ZUMA-2 试验获得批准的，该试验显示最佳总缓解率和完全缓解率分别为 91%和 68%。我们报告了在批准适应症的标准治疗环境下使用 brexu-cel 的临床结果。
纳入了 2020 年 8 月 1 日至 2021 年 12 月 31 日期间在 16 个美国机构进行白细胞分离术的患者，目的是为复发/难治性 MCL 制造商业 brexu-cel。按照标准指南收集患者数据以分析反应、结果和毒性。
在进行白细胞分离术的 189 名患者中，有 168 名（89%）接受了 brexu-cel 输注。在进行白细胞分离术的患者中，有 79%不符合 ZUMA-2 的入选标准。最佳总缓解率和完全缓解率分别为 90%和 82%。在输注后中位随访 14.3 个月时，6 个月和 12 个月无进展生存（PFS）的估计值分别为 69%（95%CI，61 至 75）和 59%（95%CI，51 至 66）。1 年时非复发死亡率为 9.1%，主要是由于感染。有 8%发生 3 级或以上细胞因子释放综合征，32%发生神经毒性。在单变量分析中，高风险简化 MCL 国际预后指数、高 Ki-67、异常、复杂核型和母细胞样/多形性变异与 brexu-cel 输注后较短的 PFS 相关。在意向治疗的单变量分析中，最近（在白细胞分离术前 24 个月内）接受苯达莫司汀治疗的患者在白细胞分离术后的 PFS 和总生存时间更短。
在标准治疗环境下，brexu-cel 的疗效和毒性与 ZUMA-2 试验报道的结果一致。MCL 的肿瘤内在特征，可能还有最近接受苯达莫司汀治疗，与较差的疗效结果相关。
