文章：

大B细胞淋巴瘤中CAR T细胞制备失败与患者预后的危险因素：英国国家CAR T专家组报告

Risk factors for CAR T-cell manufacturing failure and patient outcomes in large B-cell lymphoma: a report from the UK National CAR T Panel

原文发布日期：2025-03-04

DOI: 10.1038/s41408-025-01225-9

类型: Article

开放获取: 是

英文摘要：

CAR T-cell manufacturing failure (MF) is a situation where the manufacturing process fails to yield a product or results in one which is out-of-specification (OOS). We conducted a multicentre retrospective review of factors contributing to MF and patient outcomes. Of 981 large B-cell lymphoma (LBCL) patients approved for CAR T-cell therapy, 38 (3.87%) had MF. Eleven patients received delayed infusion with a product in-specification (delayed-infused) following 21 remanufacturing attempts. OOS product was infused in 13 (OOS-infused), and 14 were not infused. For comparison, we included 38 LBCL controls without MF; 29 received infusion (controls-infused). Prior bendamustine was the only baseline variable associated with MF risk, largely due to therapy within 6 months; 23.7% MF vs 0% controls (P = 0.0029). Overall survival (OS) and progression-free survival (PFS) were not significantly different for infused patients, with 1-year OS (PFS) of 52.8% (46.2%), 46.8% (24.2%) and 68.4% (41.4%) for OOS-infused, delayed-infused and controls-infused respectively (PFS HR OOS-infused vs controls-infused 1.41, P = 0.40; delayed-infused vs controls-infused 1.64, P = 0.25; and OOS-infused vs delayed-infused 0.86, P = 0.76). CRS, ICANS and cytopenias were not significantly different between cohorts. Outcomes for OOS-infused LBCL patients following MF are encouraging. Remanufacturing led to infusion of a product in-specification in around 50% and may be an option for patients where a suitable OOS product is not available.
 

摘要翻译： 

CAR T细胞制造失败指制造过程未能产出产品或产出的产品不符合规格。我们对导致制造失败的因素及患者结局进行了多中心回顾性分析。在981名获批接受CAR T细胞治疗的大B细胞淋巴瘤患者中，38例（3.87%）出现制造失败。其中11例患者经过21次再制造尝试后，接受了符合规格产品的延迟输注；13例患者输注了不符合规格的产品；14例未接受输注。作为对照，我们纳入了38例未出现制造失败的淋巴瘤患者，其中29例接受了输注。既往使用本伐司汀是唯一与制造失败风险相关的基线变量，主要与6个月内接受该治疗相关（制造失败组23.7% vs 对照组0%，P=0.0029）。各组输注患者的总生存期与无进展生存期无显著差异：不符合规格输注组、延迟输注组及对照输注组的1年总生存期（无进展生存期）分别为52.8%（46.2%）、46.8%（24.2%）和68.4%（41.4%）（无进展生存期风险比：不符合规格输注组 vs 对照输注组1.41，P=0.40；延迟输注组 vs 对照输注组1.64，P=0.25；不符合规格输注组 vs 延迟输注组0.86，P=0.76）。细胞因子释放综合征、免疫效应细胞相关神经毒性综合征及血细胞减少症的发生率在组间无显著差异。制造失败后接受不符合规格产品输注的淋巴瘤患者结局令人鼓舞。再制造可使约50%患者获得符合规格产品的输注，对于无法获得合适不符合规格产品的患者可能是一种可行选择。

原文链接：

Risk factors for CAR T-cell manufacturing failure and patient outcomes in large B-cell lymphoma: a report from the UK National CAR T Panel