Department of Internal Medicine and Clinical Immunology, APHP-Université-Paris-Saclay, Hôpital Universitaire Bicêtre, CHU Bicêtre, APHP, 78 rue du Général Leclerc, 94275, Le Kremlin Bicêtre, France.
INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases, 94276, Le Kremlin Bicêtre, France.
Intern Emerg Med. 2020 Jun;15(4):587-598. doi: 10.1007/s11739-020-02295-2. Epub 2020 Mar 6.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. The number of indications is increasing and antibodies targeting the CTLA-4 and PD-1/PD-L1 pathways are now also prescribed in adjuvant settings and for metastatic cancer. However, ICIs reactivate autoreactive immune cells as well as tumour-specific T cells, which lead to immune-related adverse events (irAEs) in around 70% of treated patients. Although all organs can potentially be involved, the skin, gut, thyroid, lungs, liver, and joints are most frequently affected. Most irAEs occur in the first few months of treatment but late-onset toxicity-even after the ICI has been discontinued-is also possible. In terms of severity, most irAEs are grade 1-2. Some irAEs (especially myocarditis, pneumonitis, and encephalitis) are potentially fatal; in patients with highly suggestive clinical signs, treatment should be initiated before the diagnostic work-up has been completed. When confronted with an unexpected clinical sign, the physician must differentiate rapidly between an irAE, cancer progression, and another (unrelated) cause. The management of irAEs is based on the temporary or permanent discontinuation of the ICI and (for grade ≥ 2 events) the administration of steroids.
免疫检查点抑制剂（ICIs）改变了癌症治疗格局。适应证数量不断增加，靶向 CTLA-4 和 PD-1/PD-L1 通路的抗体现在也被用于辅助治疗和转移性癌症。然而，ICIs 会重新激活自身反应性免疫细胞和肿瘤特异性 T 细胞，导致约 70%接受治疗的患者出现免疫相关不良事件（irAEs）。尽管所有器官都可能受到影响，但皮肤、肠道、甲状腺、肺、肝和关节最常受到影响。大多数 irAEs 发生在治疗的最初几个月内，但也可能出现迟发性毒性——即使在停止使用 ICI 之后。就严重程度而言，大多数 irAEs 为 1-2 级。一些 irAEs（尤其是心肌炎、肺炎和脑炎）可能是致命的；对于具有高度提示性临床体征的患者，应在完成诊断性检查之前开始治疗。当面对意外的临床体征时，医生必须快速区分 irAE、癌症进展和另一种（无关）原因。irAEs 的治疗基于 ICI 的暂时或永久停用和（对于 2 级及以上事件）类固醇的应用。
