Cancer Care Services, Princess Alexandra Hospital, Queensland, Australia.
Cancer Care Services, Princess Alexandra Hospital, Queensland, Australia.
J Thorac Oncol. 2017 Nov;12(11):1626-1635. doi: 10.1016/j.jtho.2017.08.007. Epub 2017 Aug 24.
The use of immune checkpoint inhibitor (ICI) therapy in the treatment of solid organ malignancies is becoming increasingly common. This has prompted the recognition of a new class of immune-related adverse effects (irAEs) stemming from the upregulation of T-cell activity causing autoimmunity. Neurological irAEs are a rare complication of ICIs that can lead to long-term morbidity. We report a rare case of encephalopathy after treatment with pembrolizumab, to which the patient achieved durable disease response despite discontinuation of therapy. We also review the pathophysiology, incidence, clinical presentation, diagnosis, and management of neurotoxicity secondary to ICIs. Treatment requires early administration of high-dose corticosteroids, and cessation of ICI therapy is often necessary after grade 3 or 4 irAEs. However, early data suggest that neurological irAEs correlate with a favorable disease response. Consideration should also be given to the optimal duration of ICI therapy to minimize the risk of toxicity and optimize health care expenditure.
免疫检查点抑制剂 (ICI) 在治疗实体器官恶性肿瘤中的应用越来越普遍。这促使人们认识到一类新的免疫相关不良事件 (irAE),这些不良事件源于 T 细胞活性的上调导致自身免疫。神经免疫相关不良事件是 ICI 的罕见并发症,可导致长期发病。我们报告了一例使用 pembrolizumab 治疗后发生脑病的罕见病例,尽管停止了治疗,但患者仍获得了持久的疾病缓解。我们还回顾了神经毒性的病理生理学、发生率、临床表现、诊断和管理。治疗需要早期使用大剂量皮质类固醇,并且在发生 3 级或 4 级 irAE 后通常需要停止 ICI 治疗。然而,早期数据表明,神经免疫相关不良事件与有利的疾病缓解相关。还应考虑 ICI 治疗的最佳持续时间,以最大限度地降低毒性风险并优化医疗保健支出。