CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL.
Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL.
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大多数接受CAR-T 细胞治疗(CAR-T)治疗侵袭性B细胞非霍奇金淋巴瘤(B-NHL)的患者未能获得持久缓解。已有几种新型药物获批用于治疗复发、难治性侵袭性B-NHL;然而,如何在CAR-T 治疗前后对这些疗法进行排序仍不明确。
我们进行了一项多中心回顾性分析,以描述接受CD19靶向CAR-T 治疗患者的围CAR-T 治疗实践模式和生存预测因素。研究纳入了2015年至2021年间来自13个中心接受CAR-T 治疗B-NHL的患者(n = 514)。采用Kaplan-Meier法构建生存曲线。采用多因素Cox回归分析确定各变量对生存结局的影响。对于所有接受CAR-T 治疗的患者,CAR-T 采集前更多的治疗线数和桥接治疗可预测更差的无进展生存期(PFS)和总生存期(OS)。从CAR-T 细胞输注时起算的中位PFS和OS分别为7.6个月和25.6个月。从CAR-T 后进展时起算,中位OS为5.5个月。CAR-T 失败后一线治疗的中位PFS为2.8个月。第30天仍为难治性疾病的患者OS更差,且与其他CAR-T 失败患者相比更不可能接受后续治疗。对选定患者在CAR-T 失败后任何时间进行异基因造血细胞移植,可使超过半数患者在1年时获得持久缓解。这些数据为CAR-T 细胞治疗后进展患者的未来临床试验提供了基准,该领域仍存在未满足的临床需求。
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.
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