Service et Laboratoire Central d'Hématologie, Département d'Oncologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
Nat Rev Clin Oncol. 2019 Sep;16(9):563-580. doi: 10.1038/s41571-019-0218-0.
Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.
免疫检查点抑制剂(ICIs),包括抗细胞毒性 T 淋巴细胞相关抗原 4(CTLA-4)、抗程序性死亡受体 1(PD-1)和抗程序性死亡受体 1 配体 1(PD-L1)抗体,是过去十年癌症治疗中最重要的进展之一。这些药物的适应证不断扩大到各种恶性肿瘤和疾病,从而重塑了许多以前的标准治疗方法,为患者带来了新的希望。这些进展的代价之一是出现了一系列新的免疫相关不良反应(irAEs),这些不良反应通常与经典的化疗相关毒性明显不同。由于 ICIs 在肿瘤学中的应用日益增多,临床医生将越来越多地面对常见但也罕见的 irAEs;因此,需要提高对这些毒性的临床表现、诊断和管理的认识。在这篇综述中,我们概述了迄今为止出现的各种类型的 irAEs。我们讨论了这些事件的流行病学及其动力学、危险因素、亚型和病理生理学,以及关于筛查和监测策略的新见解。我们还强调了 irAEs 管理的最重要方面。