Mirabile Aurora, Brioschi Elena, Ducceschi Monika, Piva Sheila, Lazzari Chiara, Bulotta Alessandra, Viganò Maria Grazia, Petrella Giovanna, Gianni Luca, Gregorc Vanesa
Department of Oncology, Division of Experimental Medicine, IRCCS San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
Department of Oncology, ASST Fatebenefratelli Sacco, 20121 Milan, Italy.
Cancers (Basel). 2019 Mar 1;11(3):296. doi: 10.3390/cancers11030296.
The advent of immune checkpoint inhibitors gave rise to a new era in oncology and general medicine. The increasing use of programmed death-1 (PD-1) inhibitors in non-small cell lung cancer and in other malignancies means clinicians have to face up to new challenges in managing immune-related adverse events (irAEs), which often resemble autoimmune diseases. Neurological irAEs represent an emerging toxicity related to immunotherapy, and it is mandatory to know how to monitor, recognize, and manage them, since they can rapidly lead to patient death if untreated. Guidelines for the diagnosis and treatment of these irAEs have been recently published but sharing some of the most unusual clinical cases is crucial, in our opinion, to improve awareness and to optimize the approach for these patients. A literature review on the diagnosis and treatment of immune-related neurotoxicity's has been conducted starting from the report of four cases of neurological irAEs regarding cases of polyneuropathy, myasthenia gravis, Bell's palsy, and encephalopathy, all of which occurred in oncological patients receiving PD-1 inhibitors (pembrolizumab and nivolumab) for the treatment of non-oncogene addicted advanced non-small cell lung cancer. The exclusion of other differential diagnoses and the correlation between the suspension of immunotherapy and improvement of symptoms suggest that immunotherapy could be the cause of the neurological disorders reported.
免疫检查点抑制剂的出现开启了肿瘤学和普通医学的新纪元。程序性死亡-1（PD-1）抑制剂在非小细胞肺癌和其他恶性肿瘤中的使用日益增加，这意味着临床医生在管理免疫相关不良事件（irAE）时必须面对新的挑战，这些不良事件往往类似于自身免疫性疾病。神经学上的irAE是一种与免疫治疗相关的新出现的毒性反应，必须了解如何对其进行监测、识别和管理，因为如果不进行治疗，它们可能会迅速导致患者死亡。最近已经发布了关于这些irAE诊断和治疗的指南，但我们认为，分享一些最不寻常的临床病例对于提高认识和优化对这些患者的治疗方法至关重要。从4例神经学上的irAE病例报告开始进行了一项关于免疫相关神经毒性诊断和治疗的文献综述，这些病例包括多发性神经病、重症肌无力、贝尔麻痹和脑病，所有这些病例均发生在接受PD-1抑制剂（帕博利珠单抗和纳武利尤单抗）治疗非致癌基因依赖型晚期非小细胞肺癌的肿瘤患者中。排除其他鉴别诊断以及免疫治疗的暂停与症状改善之间的相关性表明，免疫治疗可能是所报告神经疾病的病因。
