Aoun Raissa, Gratch Daniel, Kaminetzky David, Kister Ilya
Department of Neurology, NYU Grossman School of Medicine, 550 1st Ave, New York, NY, 10016, USA.
Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Icahn School of Medicine at Mount Sinai, 5 East 98th St, New York, NY, 10029, USA.
Curr Neurol Neurosci Rep. 2023 Nov;23(11):735-750. doi: 10.1007/s11910-023-01306-x. Epub 2023 Oct 23.
The use of immune checkpoint inhibitors (ICIs) for oncologic indications is associated with immune-related adverse events (irAEs). Patients with pre-existing autoimmune diseases are at increased risk of irAEs and have largely been excluded from clinical trials of ICIs. Therefore, there is limited data on the safety of safety of ICIs in patients with pre-existing neurologic autoimmune diseases (nAIDs) such as myasthenia gravis and multiple sclerosis. This review aims to synthesize the literature on the post-marketing experience with ICI in patients with pre-existing nAID and to discuss possible strategies for mitigating the risk of post-ICI nAID relapses.
Patients with pre-existing myasthenia gravis (MG), myositis, and paraneoplastic encephalitis appear highly susceptible to neurologic relapses of their underlying neurologic disorder following ICI initiation; these relapses can cause considerable morbidity and mortality. In patients with multiple sclerosis (MS), the risk and severity of MS relapses following ICI appears to be relatively lower compared to MG. Preliminary evidence suggests that older MS patients with no recent focal neuroinflammatory activity may be safely treated with ICI. Among the several case reports of ICI in patients with a history of Guillain-Barre syndrome (GBS), neurologic worsening was only recorded in one patient who was in the acute phase of GBS at the time of ICI start. Initiating an ICI in a patient with pre-existing nAID involves a complex risk-benefit discussion between the patient, their oncologist, and neurologist. Relevant issues to consider before ICI include the choice of disease-modifying therapy for nAID (if any) and strategies for promptly identifying and managing nAID relapses should they occur. Currently, the literature consists mainly of case reports and case series, subject to publication bias. Prospective studies of ICI in patients with nAID are needed to improve the level of evidence.
免疫检查点抑制剂(ICI)用于肿瘤适应症时会引发免疫相关不良事件(irAE)。患有自身免疫性疾病的患者发生irAE的风险增加,并且在很大程度上被排除在ICI的临床试验之外。因此,关于ICI在患有重症肌无力和多发性硬化症等神经系统自身免疫性疾病(nAID)患者中的安全性数据有限。本综述旨在综合关于ICI在患有nAID患者中的上市后经验的文献,并讨论减轻ICI后nAID复发风险的可能策略。
患有重症肌无力(MG)、肌炎和副肿瘤性脑炎的患者在开始使用ICI后似乎极易发生潜在神经系统疾病的神经复发;这些复发可导致相当高的发病率和死亡率。与MG相比,在多发性硬化症(MS)患者中,ICI后MS复发的风险和严重程度似乎相对较低。初步证据表明,近期无局灶性神经炎症活动的老年MS患者可能可以安全地接受ICI治疗。在几例有吉兰-巴雷综合征(GBS)病史患者使用ICI的病例报告中,仅1例在开始使用ICI时处于GBS急性期的患者记录到神经功能恶化。在患有nAID的患者中开始使用ICI需要患者、肿瘤学家和神经科医生之间进行复杂的风险-效益讨论。在使用ICI之前需要考虑的相关问题包括针对nAID的疾病修饰疗法(如果有的话)的选择,以及在nAID复发时及时识别和管理的策略。目前,文献主要由病例报告和病例系列组成,存在发表偏倚。需要对nAID患者进行ICI的前瞻性研究以提高证据水平。