Zammit François, Seront Emmanuel
Institut Roi Albert II, Department of Medical Oncology, Cliniques Universitaires Saint Luc, Avenue Hippocrate 10, 1200 Brussels, Belgium.
Pharmaceuticals (Basel). 2024 Apr 14;17(4):501. doi: 10.3390/ph17040501.
The increasing use of immune checkpoint inhibitors (ICI) in cancer therapy has brought attention to their associated neurotoxicities, termed neurological immune-related adverse events (n-irAEs). Despite their relatively rare incidence, n-irAEs pose a significant risk, potentially leading to severe, long-lasting disabilities or even fatal outcomes. This narrative review aims to provide a comprehensive overview of n-irAEs, focusing on their recognition and management. The review addresses a spectrum of n-irAEs, encompassing myositis, myasthenia gravis, various neuropathies, and central nervous system complications, such as encephalitis, meningitis, and demyelinating diseases. The key features of n-irAEs are emphasized in this review, including their early onset after initiation of ICIs, potential association with non-neurological irAEs and/or concurrent oncological response, the significance of ruling out other etiologies, and the expected improvement upon discontinuation of ICIs and/or immunosuppression. Furthermore, this review delves into considerations for ICI re-challenge and the intricate nature of n-irAEs within the context of pre-existing autoimmune and paraneoplastic syndromes. It underscores the importance of a multidisciplinary approach to diagnosis and treatment, highlighting the pivotal role of severity grading in guiding treatment decisions.
免疫检查点抑制剂(ICI)在癌症治疗中的使用日益增加,这使其相关的神经毒性受到关注,即神经免疫相关不良事件(n-irAE)。尽管其发病率相对较低,但n-irAE构成了重大风险,可能导致严重的、长期的残疾甚至致命后果。本叙述性综述旨在全面概述n-irAE,重点关注其识别和管理。该综述涉及一系列n-irAE,包括肌炎、重症肌无力、各种神经病变以及中枢神经系统并发症,如脑炎、脑膜炎和脱髓鞘疾病。本综述强调了n-irAE的关键特征,包括在开始使用ICI后早期发病、与非神经irAE和/或同时发生的肿瘤反应的潜在关联、排除其他病因的重要性以及停用ICI和/或免疫抑制后预期的改善情况。此外,本综述深入探讨了ICI再次挑战的考量因素以及在既往存在自身免疫和副肿瘤综合征背景下n-irAE的复杂性。它强调了多学科方法在诊断和治疗中的重要性,突出了严重程度分级在指导治疗决策中的关键作用。