Munir Malak, Sayed Ahmed, Addison Daniel, Epperla Narendranath
Department of Medicine, Ain Shams University Faculty of Medicine, Cairo, Egypt.
Department of Cardiology, Houston Methodist DeBakey Heart & Vascular Center, Houston, TX.
Blood Adv. 2024 Dec 24;8(24):6282-6296. doi: 10.1182/bloodadvances.2024013849.
Over the past decade, T-cell-directed therapies, including chimeric antigen receptor T-cell (CAR-T) and bispecific T-cell engager (BTE) therapies, have reshaped the treatment of an expanding number of hematologic malignancies, whereas tumor-infiltrating lymphocytes, a recently approved cellular therapy, targets solid tumor malignancies. Emerging data suggest that these therapies may be associated with a high incidence of serious cardiovascular toxicities, including atrial fibrillation, heart failure, ventricular arrhythmias, and other cardiovascular toxicities. The development of these events is a major limitation to long-term survival after these treatments. This review examines the current state of evidence, including reported incidence rates, risk factors, mechanisms, and management strategies of cardiovascular toxicities after treatment with these novel therapies. We specifically focus on CAR-T and BTE therapies and their relation to arrhythmia, heart failure, myocarditis, bleeding, and other major cardiovascular events. Beyond the relationship between cytokine release syndrome and cardiotoxicity, we describe other potential mechanisms and highlight key unanswered questions and future directions of research.
在过去十年中,针对T细胞的疗法,包括嵌合抗原受体T细胞(CAR-T)疗法和双特异性T细胞衔接器(BTE)疗法,已经重塑了越来越多血液系统恶性肿瘤的治疗方式,而肿瘤浸润淋巴细胞(一种最近获批的细胞疗法)则针对实体瘤恶性肿瘤。新出现的数据表明,这些疗法可能与严重心血管毒性的高发生率相关,包括心房颤动、心力衰竭、室性心律失常以及其他心血管毒性。这些事件的发生是这些治疗后长期生存的一个主要限制因素。本综述探讨了现有证据的现状,包括这些新型疗法治疗后心血管毒性的报告发生率、风险因素、机制以及管理策略。我们特别关注CAR-T和BTE疗法及其与心律失常、心力衰竭、心肌炎、出血和其他主要心血管事件的关系。除了细胞因子释放综合征与心脏毒性之间的关系外,我们还描述了其他潜在机制,并强调了关键的未解决问题和未来的研究方向。