免疫检查点抑制剂（ICI）治疗的患者中，报道称神经免疫相关的不良事件（n-irAEs）在所有年龄组中发生的比例高达8％。我们调查了年龄与接受ICI治疗患者之间的n-irAEs的关联，并检查了大型黑色素瘤患者队列中n-irAEs对生存结果的影响。我们对艾拉免疫肿瘤学和黑色素瘤研究所在2015年1月1日至2022年4月20日期间接受ICI治疗的晚期黑色素瘤患者进行了回顾性分析。感兴趣的结果定义为调查与年龄相关的n-irAE的频率和严重程度，ICI中断的需求，n-irAE管理所需的治疗，ICI重新引入的安全性以及n-irAE对生存的影响。共有937名患者接受ICI治疗。其中73.5％（n=689）的患者至少发生了一次IrAE。研究人群中，8％（n=76）出现了n-irAE，发作时的女性中位年龄为66岁，男性为68岁。n-irAE发作后的中位随访时间为1147天（IQR：1091.5范围：3938）。年龄在70岁以上的患者发生的irAE较少（中位数：3次事件，p=0.04，CI：2.5-4.7），而结肠炎和肺炎在18-60岁年龄组中更常见（p=0.03，95％CI：0.8、0.38，p=0.009，95％CI：0.06、0.2）。各年龄组中有35.5％的患者出现≥3级毒性反应。ICI给药到n-irAE发展的中位时间为48天。常见的n-irAE表型有肌炎（44.7％），脑炎（10.5％）和神经病变（10.5％）。 n-irAE需要住院治疗的患者占40％，并且有46％的患者需要类固醇治疗，病程诊断到类固醇治疗开始的中位数为4天。有9名患者需要二线免疫抑制治疗。再次挑战未导致71％的患者发生额外的n-irAE。发展n-irAE（HR=0.4，95％CI：0.32-0.77）或任何irAE（HR=0.7195％CI：0.56-0.88）与较长的生存期相关。神经性-irAEs是ICI的相对常见的并发症（占我们队列的8％）。与非神经性-irAE相比，老年人发生它的发展和严重性不相关。再次挑战未导致生命威胁的不良事件。发展任何irAE与较长的生存期相关，而这种关联与n-irAE更加密切。© 2023 American Academy of Neurology.

Neurological immune related adverse events (n-irAEs) reportedly occur in up to 8% of patients treated with immune-checkpoints inhibitors (ICI) of all age groups. We investigated the association between age and n-irAEs in patients treated with ICI, and examined the impact of n-irAEs on survival outcomes in a large cohort of melanoma patients.We conducted a retrospective analysis of advanced melanoma patients treated with ICI at Ella Institute for Immuno-oncology and Melanoma between 1/1/2015 and 20/04/2022. The outcomes of interest were defined as the investigation of age-related frequency and severity of n-irAE, the need for ICI interruption, the treatment required for n-irAE management, the safety of ICI reintroduction, and n-irAE's impact on survival.ICI was administered to 937 patients. At least one IrAE occurred in 73.5% (n=689) of them. Amongst the study population, 8% (n=76) developed a n-irAE, with a median age of 66 in females and 68 in males at onset. Median follow-up after n-irAE was 1,147 days (IQR: 1091.5 range: 3938). Fewer irAEs occurred in patients older than 70 years (median: 3 events, p=0.04, CI:2.5-4.7), while specifically colitis and pneumonitis were more common in the 18-60 age group (p=0.03 95% CI:0.8,0.38, p=0.009, 95% CI:0.06,0.2). Grade ≥ 3 toxicity was seen in 35.5% of patients across age groups. Median time from ICI administration to n-irAE development was 48 days across age groups. Common n-irAE phenotypes were myositis (44.7%), encephalitis (10.5%), and neuropathy (10.5%). N-irAE required hospitalization in 40% of patients, and steroids treatment in 46% with a median of 4 days from n-irAE diagnosis to steroids treatment initiation. Nine patients needed second-line immunosuppressive treatment. Rechallenge did not cause additional n-irAE in 71% of patients. Developing n-irAE (HR=0.4, 95% CI:0.32,0.77) or any irAE (HR=0.7195% CI:0.56,0.88) were associated with longer survival.Neurological-irAEs are a relatively common complication of ICI (8% of our cohort). Older age was not associated with its development or severity, in contrast with non-neurological-irAE which occurred less frequently in the elderly. Rechallenge did not result in life-threatening AEs. Development of any irAE was associated with longer survival, this association was stronger with n-irAE.© 2023 American Academy of Neurology.