Ganatra Sarju, Dani Sourbha S, Yang Eric H, Zaha Vlad G, Nohria Anju
Cardio-Oncology Program, Division of Cardiovascular Medicine, Department of Medicine, Lahey Hospital & Medical Center, Burlington, Massachusetts, USA.
Division of Cardiology, Department of Medicine, UCLA-Cardio-Oncology Program, University of California-Los Angeles, Los Angeles, California, USA.
JACC CardioOncol. 2022 Dec 20;4(5):616-623. doi: 10.1016/j.jaccao.2022.07.014. eCollection 2022 Dec.
T-cell therapies, such as chimeric antigen receptor (CAR) T-cell, bispecific T-cell engager (BiTE) and tumor-infiltrating lymphocyte (TIL) therapies, fight cancer cells harboring specific tumor antigens. However, activation of the immune response by these therapies can lead to a systemic inflammatory response, termed cytokine release syndrome (CRS), that can result in adverse events, including cardiotoxicity. Retrospective studies have shown that cardiovascular complications occur in 10% to 20% of patients who develop high-grade CRS after CAR T-cell therapy and can include cardiomyopathy, heart failure, arrhythmias, and myocardial infarction. While cardiotoxicities have been less commonly reported with BiTE and TIL therapies, systematic surveillance for cardiotoxicity has not been performed. Patients undergoing T-cell therapies should be screened for cardiovascular conditions that may not be able to withstand the hemodynamic perturbations imposed by CRS. Generalized management of CRS, including the use of the interleukin-6 antagonist, tocilizumab, for high-grade CRS, is used to mitigate the risk of cardiotoxicity.
T细胞疗法,如嵌合抗原受体(CAR)T细胞疗法、双特异性T细胞衔接器(BiTE)疗法和肿瘤浸润淋巴细胞(TIL)疗法,可对抗携带特定肿瘤抗原的癌细胞。然而,这些疗法激活免疫反应可导致一种全身性炎症反应,称为细胞因子释放综合征(CRS),这可能会引发不良事件,包括心脏毒性。回顾性研究表明,在接受CAR T细胞疗法后发生重度CRS的患者中,10%至20%会出现心血管并发症,可能包括心肌病、心力衰竭、心律失常和心肌梗死。虽然BiTE和TIL疗法导致心脏毒性的报道较少,但尚未对心脏毒性进行系统监测。接受T细胞疗法的患者应筛查可能无法承受CRS引起的血流动力学紊乱的心血管疾病。CRS的一般管理措施,包括使用白细胞介素-6拮抗剂托珠单抗治疗重度CRS,用于降低心脏毒性风险。