Unit of Endocrinology, Department of Clinical and Experimental Medicine, Building H, Floor 4, "G. Martino" University Hospital, University of Messina, 98125, Messina, Italy.
Unit of Nuclear Medicine, Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy.
J Endocrinol Invest. 2019 Jul;42(7):745-756. doi: 10.1007/s40618-018-0984-z. Epub 2018 Nov 23.
Immune checkpoint inhibitors (ICIs) are novel anticancer agents, recently introduced with the aim of boosting the immune response against tumors. ICIs are monoclonal autoantibodies that specifically target inhibitory receptors on T cells: cytotoxic T lymphocyte antigen 4 (CTLA4), programmed death 1 (PD-1) and its ligand (PD-1L). ICIs also generate peculiar dysimmune toxicities, called immune-related adverse events (irAEs), that can potentially affect any tissue, and some may be life-threatening if not promptly recognized. The endocrine and metabolic side effects of ICIs are reviewed here, with a particular focus on their clinical presentation and management. They are among the most frequent toxicities (around 10%) and include hypophysitis, thyroid disorders, adrenalitis, and diabetes mellitus. Treatment is based on the replacement of specific hormone deficits, accompanied by immunosuppression (with corticosteroids or other drugs), depending on irAEs grade, often without the need of ICI withdrawal, except in more severe forms. Prompt recognition of endocrine and metabolic irAEs and adequate treatment allow the patients to continue a therapy they are benefiting from. Endocrinologists, as an integral part of the multidisciplinary oncologic team, need to be familiar with the unique toxicity profile of these anticancer agents. Practical recommendations for their management are proposed.
免疫检查点抑制剂(ICIs)是一类新型的抗癌药物,最近被引入以增强针对肿瘤的免疫反应。ICIs 是特异性靶向 T 细胞抑制性受体的单克隆自身抗体:细胞毒性 T 淋巴细胞抗原 4(CTLA4)、程序性死亡受体 1(PD-1)及其配体(PD-1L)。ICIs 还会产生特殊的免疫毒性,称为免疫相关不良事件(irAEs),这些毒性可能会影响任何组织,如果不能及时识别,有些毒性可能会危及生命。本文综述了 ICI 的内分泌和代谢副作用,特别关注其临床表现和管理。它们是最常见的毒性之一(约 10%),包括垂体炎、甲状腺疾病、肾上腺炎和糖尿病。治疗基于特定激素缺乏的替代,同时根据 irAEs 分级进行免疫抑制(使用皮质类固醇或其他药物),通常无需停止 ICI 治疗,除非出现更严重的情况。及时识别内分泌和代谢性 irAEs 并进行适当治疗可使患者继续受益于他们正在接受的治疗。内分泌学家作为多学科肿瘤团队的一部分,需要熟悉这些抗癌药物的独特毒性特征。本文提出了针对这些毒性的管理的实用建议。