Department of Translational Medical Sciences, Federico II University, Naples, Italy.
Department of Public Health, Section of Hygiene, University of Naples Federico II, Naples, Italy.
Expert Opin Drug Saf. 2021 Jun;20(6):685-694. doi: 10.1080/14740338.2021.1906860. Epub 2021 Apr 1.
: Cancer immunotherapies with monoclonal antibodies (mAbs) against immune checkpoints (i.e. CTLA-4 and PD-1/PD-L1) have revolutionized antineoplastic treatments. Immune checkpoint inhibitors (ICIs) approved for cancer immunotherapy are mAbs anti-CTLA-4 (ipilimumab), anti-PD-1 (nivolumab, pembrolizumab, and cemiplimab), and anti-PD-L1 (atezolizumab, avelumab, and durvalumab). Treatment with ICIs can be associated with immune-related adverse events (irAEs), including an increased risk of developing myocarditis. These findings are compatible with the observation that, CTLA-4, PD-1, and PD-L1 pathways play a central role in the modulation of autoimmunity.: In this paper, we start from examining the pathogenesis of cardiovascular adverse events from ICIs, and then we focus on risk factors and strategies to prevent and manage this cardiotoxicity.: There is a growing need for a multidisciplinary approach of ICI-associated cardiotoxicity, involving oncologists, cardiologists, and immunologists. Prevention and effective management of ICIs cardiotoxicity starts with an in-depth screening and surveillance strategies of high-risk patients, in order to improve early detection and appropriate management in a personalized approach.
癌症免疫疗法中使用单克隆抗体(mAbs)针对免疫检查点(即 CTLA-4 和 PD-1/PD-L1)已经彻底改变了抗肿瘤治疗。已批准用于癌症免疫疗法的免疫检查点抑制剂(ICI)是 mAbs 抗 CTLA-4(伊匹单抗)、抗 PD-1(纳武利尤单抗、帕博利珠单抗和西米普利单抗)和抗 PD-L1(阿替利珠单抗、avelumab 和度伐鲁单抗)。ICI 治疗可能与免疫相关的不良反应(irAEs)相关,包括心肌炎发生风险增加。这些发现与 CTLA-4、PD-1 和 PD-L1 途径在自身免疫调节中发挥核心作用的观察结果一致。在本文中,我们首先从检查 ICI 引起的心血管不良事件的发病机制开始,然后重点讨论预防和管理这种心脏毒性的危险因素和策略。对于 ICI 相关的心脏毒性,需要多学科的方法,涉及肿瘤学家、心脏病学家和免疫学家。预防和有效管理 ICI 心脏毒性始于对高危患者进行深入的筛查和监测策略,以便在个性化治疗中提高早期检测和适当管理的能力。