Department of Medicine, Vanderbilt University School of Medicine, Nashville, USA.
Department of Medicine, Vanderbilt University Medical Center, Nashville, USA.
Expert Rev Clin Immunol. 2023 Jul-Dec;19(9):1117-1129. doi: 10.1080/1744666X.2023.2221434. Epub 2023 Jun 5.
Immune checkpoint inhibitors (ICIs) have become a pillar of treatment for numerous cancers with increasing use in combination with other ICIs and in earlier stages of disease treatment. Although effective, ICI use is accompanied by a milieu of potentially bothersome or even life-threatening toxicities known as immune-related adverse events (irAEs), necessitating careful monitoring and early intervention.
In this review, we provide an overview of recent advances surrounding toxicity pathophysiology and treatment in the context of relevant organ systems. An emphasis on current treatments by toxicity, as well as updates on steroid-refractory toxicities, chronic toxicities, and biomarkers will be a focus of this update on the current understanding of irAEs.
ICI toxicities are a major limitation on the deployment of multi-agent ICI regimens and are thus a major priority to understand, treat, and prevent. Recent developments have led to greater understanding of the pathophysiology of these events, which may lead to improved prevention or mitigation strategies. Further, early studies have also suggested steroid-sparing approaches that may be useful. Ultimately, preventing and managing irAEs will be a key goal toward successful ICI treatment across a broader range of patients with cancer.
免疫检查点抑制剂（ICI）已成为治疗多种癌症的重要手段，其应用日益广泛，包括与其他 ICI 联合使用以及在疾病治疗的早期阶段。尽管有效，但 ICI 的使用伴随着一系列潜在的麻烦甚至危及生命的毒性，称为免疫相关不良事件（irAEs），需要仔细监测和早期干预。
在这篇综述中，我们概述了与相关器官系统背景下毒性发病机制和治疗相关的最新进展。本文重点介绍了当前按毒性分类的治疗方法，以及对类固醇难治性毒性、慢性毒性和生物标志物的更新，这是对 irAEs 现有认识的最新更新。
ICI 毒性是限制多药物 ICI 方案应用的主要因素，因此是需要理解、治疗和预防的主要重点。最近的发展使人们对这些事件的病理生理学有了更深入的了解，这可能会导致改进预防或缓解策略。此外，早期研究还提出了可能有用的类固醇节约方法。最终，预防和管理 irAEs 将是成功治疗更广泛癌症患者的关键目标。
