Lefebvre Bénédicte, Kang Yu, Vakilpour Azin, Onoue Takeshi, Frey Noelle V, Brahmbhatt Priya, Huang Brian, Oladuja Kemi, Koropeckyj-Cox Daniel, Wiredu Courteney, Smith Amanda M, Chittams Jesse, Carver Joseph, Scherrer-Crosbie Marielle
Division of Cardiovascular Diseases, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Division of Hematology and Oncology Diseases, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
JACC CardioOncol. 2023 Oct 10;5(6):747-754. doi: 10.1016/j.jaccao.2023.07.009. eCollection 2023 Dec.
Previous retrospective studies have shown that chimeric antigen receptor T (CAR-T) cell therapy may be associated with major adverse cardiovascular events (MACE), especially in the context of cytokine-release syndrome (CRS) events.
The aim of this prospective observational study was to define the occurrence of MACE in adults undergoing treatment with CAR-T cell therapy and identify associated risk factors.
Vital signs, blood samples, and an echocardiogram were collected prior to and 2 days, 1 week, 1 month, and 6 months after CAR-T cell infusion, and charts were consulted at 12 months. In the event of CRS, echocardiography was repeated within 72 hours. MACE were defined as cardiovascular death, symptomatic heart failure, acute coronary syndrome, ischemic stroke, and de novo cardiac arrhythmia.
A total of 44 patients were enrolled (mean age 58 ± 11 years, 77% men). The median follow-up duration was 487 days (Q1-Q3: 258-622 days). There were 24 episodes of CRS in 23 patients (52%) (13 grade 1, 10 grade 2, and 1 grade 3), with a median time to CRS of 4 days. Two patients had MACE (heart failure with preserved ejection fraction and atrial fibrillation) within 1 year and 6 and 7 days after CAR-T cell infusion. There was no change in left ventricular ejection fraction, but a modest decrease in global longitudinal strain was noted.
There were few cardiac effects associated with contemporary CAR-T cell therapy. As MACE occurred after CRS episodes, aggressive treatment and close follow-up during CRS events are essential.
既往回顾性研究表明，嵌合抗原受体T（CAR-T）细胞疗法可能与主要不良心血管事件（MACE）相关，尤其是在细胞因子释放综合征（CRS）事件的背景下。
这项前瞻性观察性研究的目的是确定接受CAR-T细胞疗法治疗的成人中MACE的发生率，并确定相关危险因素。
在CAR-T细胞输注前以及输注后2天、1周、1个月和6个月收集生命体征、血样和超声心动图，并在12个月时查阅病历。发生CRS时，在72小时内重复进行超声心动图检查。MACE定义为心血管死亡、有症状的心力衰竭、急性冠状动脉综合征、缺血性中风和新发心律失常。
共纳入44例患者（平均年龄58±11岁，77%为男性）。中位随访时间为487天（四分位间距：258-622天）。23例患者（52%）发生24次CRS发作（13例1级，10例2级，1例3级），CRS的中位发生时间为4天。2例患者在CAR-T细胞输注后1年内以及6天和7天出现MACE（射血分数保留的心力衰竭和心房颤动）。左心室射血分数无变化，但整体纵向应变有适度下降。
当代CAR-T细胞疗法相关的心脏影响较少。由于MACE在CRS发作后发生，因此在CRS事件期间积极治疗和密切随访至关重要。
