Cardiovascular Events Among Adults Treated With Chimeric Antigen Receptor T-Cells (CAR-T)
Cardiovascular Events Among Adults Treated With Chimeric Antigen Receptor T-Cells (CAR-T)
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DOI：
10.1016/j.jacc.2019.10.038
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发表时间：
2019-12-24
影响因子：
24
通讯作者：
Neilan, Tomas G.
中科院分区：
文献类型：
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作者：
Alvi, Raza M.;Frigault, Matthew J.;Neilan, Tomas G.
嵌合抗原受体引导T细胞（CAR-T）靶向癌细胞。在接受CAR-T治疗的成年人中，心脏毒性和心血管（CV）事件的数据有限。目的：本研究的目的是评估CAR-T可能的心脏毒性。方法：纳入137例接受CAR-T治疗的患者。协变量包括细胞因子释放综合征（CRS）的发生和等级以及托珠单抗治疗CRS的使用情况。心脏毒性被定义为左心室射血分数降低或血清肌钙蛋白升高。心血管事件是心律失常、失代偿性心力衰竭和心血管死亡的复合。结果中位年龄为62岁（四分位间距[IQR]: 54 ~ 70岁），67%为男性，88%为淋巴瘤，8%为骨髓瘤。大约50%的患者接受商业化CAR-T治疗（Yescarta或Kymriah），其余患者接受非商业产品治疗。CAR-T后发生CRS的中位时间为5天（IQR: 2 - 7天），59%发生CRS， 39%为2级。56例CRS患者（41%）在发病后27小时（IQR: 16至48小时）接受Tocilizumab治疗。53例患者中有29例（54%）出现肌钙蛋白升高，29例患者中有8例（28%）出现左心室射血分数降低；仅发生在>= 2级CRS患者中。有17例心血管事件（12%，6例心血管死亡，6例失偿性心力衰竭，5例心律失常；事件发生的中位时间为21天），均发生在>= 2级CRS(31%的患者发生>= 2级CRS)， 95%的事件发生在肌钙蛋白升高后。CRS发病和托珠单抗用药之间的持续时间与CV事件相关，每延迟12小时，风险增加1.7倍。结论：在成人中，car - t后心脏损伤和心血管事件很常见。CRS、肌钙蛋白升高和CV事件之间存在分级关系，从CRS发病到托珠单抗的时间较短与较低的CV事件发生率相关。(C) 2019年由美国心脏病学会基金会发布。
BACKGROUND Chimeric antigen receptors redirect T cells (CAR-T) to target cancer cells. There are limited data characterizing cardiac toxicity and cardiovascular (CV) events among adults treated with CAR-T.OBJECTIVES The purpose of this study was to evaluate the possible cardiac toxicities of CAR-T.METHODS The registry included 137 patients who received CAR-T. Covariates included the occurrence and grade of cytokine release syndrome (CRS) and the administration of tocilizumab for CRS. Cardiac toxicity was defined as a decrease in the left ventricular ejection fraction or an increase in serum troponin. Cardiovascular events were a composite of arrhythmias, decompensated heart failure, and CV death.RESULTS The median age was 62 years (interquartile range [IQR]: 54 to 70 years), 67% were male, 88% had lymphoma, and 8% had myeloma. Approximately 50% were treated with commercial CAR-T (Yescarta or Kymriah), and the remainder received noncommercial products. CRS, occurring a median of 5 days (IQR: 2 to 7 days) after CAR-T, occurred in 59%, and 39% were grade $2. Tocilizumab was administered to 56 patients (41%) with CRS, at a median of 27 h (IQR: 16 to 48 h) after onset. An elevated troponin occurred in 29 of 53 tested patients (54%), and a decreased left ventricular ejection fraction in 8 of 29 (28%); each occurred only in patients with grade >= 2 CRS. There were 17 CV events (12%, 6 CV deaths, 6 decompensated heart failure, and 5 arrhythmias; median time to event of 21 days), all occurred with grade >= 2 CRS (31% patients with grade > 2 CRS), and 95% of events occurred after an elevated troponin. The duration between CRS onset and tocilizumab administration was associated with CV events, where the risk increased 1.7-fold with each 12-h delay to tocilizumab.CONCLUSIONS Among adults, cardiac injury and CV events are common post-CAR-T. There was a graded relationship among CRS, elevated troponin, and CV events, and a shorter time from CRS onset to tocilizumab was associated with a lower rate of CV events. (C) 2019 by the American College of Cardiology Foundation.