Department of Medicine, Carbone Cancer Center, University of Wisconsin, Madison, WI.
Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
Blood Adv. 2023 Jun 27;7(12):2657-2669. doi: 10.1182/bloodadvances.2022008240.
Most patients receiving chimeric antigen receptor T-cell therapy (CAR-T) for aggressive B-cell non-Hodgkin lymphoma (B-NHL) do not experience a durable remission. Several novel agents are approved to treat relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre- and post-CAR-T. We conducted a multicenter retrospective analysis to describe peri-CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n = 514) from 13 centers treated with CAR-T for B-NHL between 2015-2021 were included in the study. Survival curves were constructed using Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of the variables on survival outcomes. For all patients receiving CAR-T, a greater number of lines of therapy pre-CAR-T apheresis and bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). The median PFS and OS from the time of CAR-T cell infusion were 7.6 and 25.6 months, respectively. From the time of progression post-CAR-T, the median OS was 5.5 months. The median PFS of treatments administered in the first-line post-CAR-T failure was 2.8 months. Patients with refractory disease on day 30 had inferior OS and were less likely to receive subsequent treatment(s) than other patients with CAR-T failure. Allogeneic hematopoietic cell transplantation for selected patients at any time following CAR-T failure led to durable responses in over half of patients at 1 year. These data provide a benchmark for future clinical trials in patients with post-CAR-T cell progression, which remains an unmet clinical need.
大多数接受嵌合抗原受体 T 细胞疗法(CAR-T)治疗侵袭性 B 细胞非霍奇金淋巴瘤(B-NHL)的患者并未经历持久缓解。有几种新型药物被批准用于治疗复发、难治性侵袭性 B-NHL;然而,在接受 CAR-T 治疗前后如何对这些疗法进行排序仍不清楚。我们进行了一项多中心回顾性分析,以描述接受 CD19 定向 CAR-T 治疗的患者接受 CAR-T 治疗前后的围 CAR-T 治疗模式和生存预测因素。该研究纳入了 2015 年至 2021 年间,13 个中心接受 CAR-T 治疗的 B-NHL 患者(n=514)。使用 Kaplan-Meier 方法构建生存曲线。使用多变量 Cox 回归分析确定这些变量对生存结果的影响。对于所有接受 CAR-T 的患者,在接受 CAR-T 前的细胞分离和桥接治疗中,治疗线数越多,无进展生存(PFS)和总生存(OS)越差。从 CAR-T 细胞输注时间开始,中位 PFS 和 OS 分别为 7.6 个月和 25.6 个月。从 CAR-T 后进展开始,中位 OS 为 5.5 个月。在 CAR-T 失败后的一线治疗中,中位 PFS 为 2.8 个月。在 CAR-T 失败后第 30 天疾病处于难治状态的患者 OS 较差,并且比其他 CAR-T 失败患者更不可能接受后续治疗。对于任何时间因 CAR-T 失败而选择的患者,同种异体造血细胞移植均可导致超过一半的患者在 1 年内获得持久缓解。这些数据为 CAR-T 细胞后进展患者的未来临床试验提供了基准,这仍然是一个未满足的临床需求。