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免疫检查点抑制剂再挑战的神经毒性和安全性:神经肿瘤学实践中的一个日益严重的问题。

Neurotoxicity and safety of the rechallenge of immune checkpoint inhibitors: a growing issue in neuro-oncology practice.

机构信息

Neuro-Oncology Unit, Neurology Department, Hospital Universitari de Bellvitge-Institut Català d Oncologia L'Hospitalet, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, C/Feixa Llarga S/N, 08907, L'Hospitalet, Barcelona, Spain.

Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain.

出版信息

Neurol Sci. 2022 Apr;43(4):2339-2361. doi: 10.1007/s10072-022-05920-4. Epub 2022 Feb 17.

DOI:10.1007/s10072-022-05920-4
PMID:35175441
Abstract

Neurological, immune-related adverse events (n-irAE) due to immune checkpoint inhibitors (ICI) represent a growing clinical problem in neuro-oncology practice. Although rare, the frequency of n-irAEs will increase as ICI use becomes more common. Central and peripheral nervous systems may be involved, and multiple n-irAEs like myositis, myasthenia gravis, and myocarditis can arise in the same patient. Prompt recognition, initial ICI discontinuation, and treatment with immunosuppressive therapy comprise key aspects of managing these potentially fatal neurological complications. Severe and/or treatment-refractory n-irAEs may occur and require individualized care. In the same vein, a possible reintroduction of ICI after a n-irAE represents an additional challenge in clinical practice. An approach by experienced neurologists involved in highly subspecialized, multidisciplinary care teams is, therefore, of major importance in managing these cases. The present study updates current knowledge regarding presentation forms, diagnostic workflows, outcomes, and general management of n-irAEs. With the aim to guide neurologists in decision-making processes during such scenarios, the study further reviews available data on ICI reintroduction safety in patients with prior n-irAEs.

摘要

由于免疫检查点抑制剂(ICI)引起的神经免疫相关不良事件(n-irAE)是神经肿瘤学实践中日益严重的临床问题。尽管罕见,但随着 ICI 的使用越来越普遍,n-irAE 的频率将会增加。中枢和外周神经系统都可能受到影响,同一患者可能会出现多种 n-irAE,如肌炎、重症肌无力和心肌炎。及时识别、初始 ICI 停药以及免疫抑制治疗是管理这些潜在致命性神经并发症的关键方面。严重和/或治疗抵抗性 n-irAE 可能发生,需要个体化治疗。同样,在 n-irAE 后再次引入 ICI 也代表了临床实践中的另一个挑战。因此,由参与高度专业化、多学科护理团队的经验丰富的神经科医生提供的治疗方法对于管理这些病例至关重要。本研究更新了目前关于 n-irAE 的表现形式、诊断流程、结局和一般管理的知识。为了指导神经科医生在这种情况下做出决策,本研究进一步回顾了先前存在 n-irAE 的患者中再次引入 ICI 的安全性相关数据。

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Absence of significant clinical benefit for a systematic routine creatine phosphokinase measurement in asymptomatic patients treated with anti-programmed death protein (ligand) 1 immune checkpoint inhibitor to screen cardiac or neuromuscular immune-related toxicities.
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