Simbaqueba Cesar Clavijo, Aponte Maria Patarroyo, Kim Peter, Deswal Anita, Palaskas Nicolas L, Iliescu Cezar, Jahangir Eiman, Yang Eric H, Steiner Raphael E, Lopez-Mattei Juan
Department of General Internal Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Cardiology, University of Texas Health System, Memorial Hermann Hospital, Houston, Texas.
J Immunother Precis Oncol. 2020 Jul 20;3(3):113-120. doi: 10.36401/JIPO-20-10. eCollection 2020 Aug.
In recent years, cancer treatment has evolved, and new therapies have been introduced with significant improvement in prognosis. The immunotherapies stand out owing to their efficacy and remission rate. Chimeric antigen receptor (CAR) T-cell therapy is a part of this new era of therapies. Chimeric antigen receptor T-cell therapy is a form of adoptive cellular therapy that uses a genetically encoded CAR in modified human T cells to target specific tumor antigens in a nonconventional, non-major histocompatibility complex (MHC) protein presentation. Chimeric antigen receptor T-cell therapy successfully identifies tumor antigens and through activation of T cells destroys tumoral cells. It has been found to efficiently induce remission in patients who have been previously treated for B-cell malignancies and have persistent disease. As the use of this novel therapy increases, its potential side effects also have become more evident, including major complications like cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokine release syndrome is a major systemic inflammatory process as a result of massive cytokine production by the proliferating and activated CAR T cells in which multiple interleukins and immune cells contribute to the inflammatory response. Cytokine release syndrome has been associated with cardiovascular life-threatening complications including hypotension, shock, tachycardia, arrhythmias, left ventricular dysfunction, heart failure, and cardiovascular death. Arrhythmias, among its major complications, vary from asymptomatic prolonged corrected QT interval (QTc) to supraventricular tachycardia, atrial fibrillation, flutter, and ventricular arrhythmias like Torsade de pointes. This article focuses on the cardiovascular complications and arrhythmias associated with CRS and CAR T-cell therapy.
近年来，癌症治疗不断发展，新疗法相继问世，预后有了显著改善。免疫疗法因其疗效和缓解率而备受瞩目。嵌合抗原受体（CAR）T细胞疗法是这一新时代疗法的一部分。嵌合抗原受体T细胞疗法是一种过继性细胞疗法，它在经过改造的人类T细胞中使用基因编码的CAR，以非常规的、非主要组织相容性复合体（MHC）蛋白呈递方式靶向特定肿瘤抗原。嵌合抗原受体T细胞疗法成功识别肿瘤抗原，并通过激活T细胞来破坏肿瘤细胞。已发现它能有效诱导曾接受过B细胞恶性肿瘤治疗且疾病持续存在的患者实现缓解。随着这种新型疗法使用的增加，其潜在的副作用也变得更加明显，包括细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）等主要并发症。细胞因子释放综合征是一种主要的全身性炎症过程，是由于增殖和激活的CAR T细胞大量产生细胞因子所致，其中多种白细胞介素和免疫细胞参与了炎症反应。细胞因子释放综合征与危及生命的心血管并发症相关，包括低血压、休克、心动过速、心律失常、左心室功能障碍、心力衰竭和心血管死亡。心律失常是其主要并发症之一，从无症状的校正QT间期（QTc）延长到室上性心动过速、心房颤动、扑动以及尖端扭转型室性心动过速等室性心律失常不等。本文重点关注与CRS和CAR T细胞疗法相关的心血管并发症和心律失常。
