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我们如何管理免疫检查点抑制剂的心脏毒性?

How can we manage the cardiac toxicity of immune checkpoint inhibitors?

机构信息

Department of Translational Medical Sciences, Federico II University, Naples, Italy.

Department of Public Health, Section of Hygiene, University of Naples Federico II, Naples, Italy.

出版信息

Expert Opin Drug Saf. 2021 Jun;20(6):685-694. doi: 10.1080/14740338.2021.1906860. Epub 2021 Apr 1.

Abstract

: 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.

摘要

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。

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