Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA.
Eur J Neurol. 2023 Oct;30(10):3221-3227. doi: 10.1111/ene.15942. Epub 2023 Jul 2.
Little is known about risk factors for developing neurological immunological adverse events (neuro-irAEs) from immune checkpoint inhibitors (ICIs). We report the incidence, predictors for development, impact on mortality of neuro-irAEs, and impact of ICIs on pre-existing neurological conditions in a large clinical cohort.
Patients who received ICIs between January 2011 and December 2018 were identified from a tertiary cancer center registry. Descriptive statistics were used to summarize patient, cancer, and treatment data. Odds ratios from univariable and multivariable logistic regression models were calculated to identify potential predictors for developing a neuro-irAE. Impact of neuro-irAEs on overall survival was estimated by Kaplan-Meier and Cox proportional hazard models.
Overall frequency of neurological irAEs was 2.3%. Peripheral nervous system complications were most frequent (53.6%). Melanoma, younger age, prior chemotherapy, prior resection, CTLA-4 ICIs exposure, and combination PD-1 and CTLA-4 ICIs exposure had significantly higher odds for developing a neuro-irAE (p < 0.05) in univariate but not multivariate models. Those with a neuro-irAE were less likely to die at 3 years compared to those without a neuro-irAE (69% vs. 55%, p = 0.004) in univariate but not multivariate model. Flare of pre-existing neurological condition after exposure to ICIs was present (15.4%, 2 of 13 patients) but manageable. One patient was rechallenged with ICIs without recurrent flare.
Neuro-irAEs are not associated with increase in overall mortality. Potential predictors for the development of neuro-irAEs are younger age, melanoma, prior chemotherapy and resection, CTLA-4, or combination ICIs exposure.
对于免疫检查点抑制剂（ICI）引发的神经免疫不良事件（neuro-irAEs）的发病风险因素，人们知之甚少。我们报告了在一个大型临床队列中，ICI 治疗患者的 neuro-irAE 发病率、发病预测因素、对死亡率的影响以及对预先存在的神经系统疾病的影响。
从一家三级癌症中心的登记处确定了 2011 年 1 月至 2018 年 12 月期间接受 ICI 治疗的患者。采用描述性统计方法总结患者、癌症和治疗数据。采用单变量和多变量逻辑回归模型计算比值比，以确定发生 neuro-irAE 的潜在预测因素。通过 Kaplan-Meier 和 Cox 比例风险模型估计 neuro-irAE 对总生存的影响。
神经系统免疫不良事件的总体发生率为 2.3%。周围神经系统并发症最常见（53.6%）。单变量分析中，黑色素瘤、年龄较小、先前化疗、先前切除、CTLA-4 ICI 暴露以及 PD-1 和 CTLA-4 ICI 联合暴露与发生 neuro-irAE 的可能性显著相关（p<0.05），但多变量分析中则无此相关性。在单变量模型中，发生 neuro-irAE 的患者与未发生 neuro-irAE 的患者相比，3 年时死亡的可能性较低（69% vs. 55%，p=0.004），但在多变量模型中则无此相关性。ICI 治疗后预先存在的神经系统疾病出现“ flares”（15.4%，13 例中有 2 例），但可以控制。1 例患者再次接受 ICI 治疗，未出现再次 flares。
neuro-irAE 与总死亡率的增加无关。发生 neuro-irAE 的潜在预测因素为年龄较小、黑色素瘤、先前化疗和切除、CTLA-4 或联合 ICI 暴露。
