Purpose: Evaluation of predictors and outcomes in NSCLC patients treated with an immune checkpoint inhibitor (ICI) following a severe immune-related adverse event (irAE). Methods: We included all NSCLC patients receiving ≥1 ICI cycle and corticosteroids for CTCAE Grade ≥3 irAEs between 2017 and 2023 from three UK NHS teaching hospitals. Progression-free survival (PFS) and overall survival (OS) after the 1st irAE, best overall response (BOR) to ICI, and predictors of clinical benefit were evaluated. Kaplan–Meier, Cox and logistic regression models, and Wilcoxon tests were used. Results: We screened 1658 NSCLC patients and identified 80 eligible subjects. The majority of patients had metastatic (n= 50, 63%) vs. localized (n= 30, 37%) NSCLC. Most patients developed a single ≥Grade 3 irAE on 1st line ICI (n= 71, 89%). Overall, 14 (18%) patients developed 2nd irAEs, 7 after rechallenge with ICIs. In the complete cohort, median OS after 1st irAE was 15.84 months (95% CI, 12.45–26.91). Lower neutrophil-to-lymphocyte ratio (NLR), patients receiving >4 cycles of ICI or median duration of ICI of >2.76 months before 1st irAE were associated with improved OS (p< 0.05), the latter two with PFS (p< 0.05). Age, gender, stage,KRASmutation, PD-L1 and ICI type were not associated with PFS or OS. Pneumonitis as 1st irAE had the worst PFS and OS (p< 0.05). Median starting corticosteroid dose of ≤60 mg for 1st irAE had an improved OS (p= 0.04). Post 1st irAE response associated with better PFS and OS (p< 0.05). Number and duration of irAEs and additional immunosuppressive agents (14% of patients) were not associated with PFS or OS. Conclusions: In ≥Grade 3 irAEs patients managed with corticosteroids, lower baseline NLR, longer ICI use, response to ICI after 1st irAE, and a ≤60 mg corticosteroid dose had promising outcomes.
目的：评估非小细胞肺癌（NSCLC）患者在发生严重免疫相关不良事件（irAE）后接受免疫检查点抑制剂（ICI）治疗的预测因素及临床结局。方法：本研究纳入2017年至2023年间英国三家国民医疗服务体系教学医院中所有接受≥1周期ICI治疗、并因CTCAE≥3级irAE接受皮质类固醇治疗的NSCLC患者。评估指标包括首次irAE后的无进展生存期（PFS）和总生存期（OS）、ICI最佳总体缓解率（BOR）以及临床获益的预测因素。采用Kaplan-Meier法、Cox回归模型、逻辑回归模型及Wilcoxon检验进行统计分析。结果：共筛查1658例NSCLC患者，最终纳入80例符合条件者。其中转移性NSCLC患者占多数（n=50，63%），局部晚期患者占37%（n=30）。大多数患者（n=71，89%）在一线ICI治疗期间发生单次≥3级irAE。总体而言，14例（18%）患者出现第二次irAE，其中7例发生在重启ICI治疗后。全队列患者首次irAE后中位OS为15.84个月（95% CI：12.45-26.91）。较低的中性粒细胞-淋巴细胞比值（NLR）、接受>4周期ICI治疗或首次irAE前ICI中位治疗时长>2.76个月与OS改善显著相关（p<0.05），后两个因素亦与PFS改善相关（p<0.05）。年龄、性别、分期、KRAS突变、PD-L1表达及ICI类型与PFS或OS无显著相关性。以肺炎为首发irAE的患者PFS与OS最差（p<0.05）。首次irAE皮质类固醇起始剂量中位数≤60 mg的患者OS更优（p=0.04）。首次irAE后出现治疗应答与更好的PFS和OS相关（p<0.05）。irAE发生次数、持续时间及额外免疫抑制剂使用（14%患者）与PFS或OS无显著关联。结论：在皮质类固醇治疗的≥3级irAE患者中，较低的基线NLR、较长的ICI治疗时间、首次irAE后对ICI的应答反应以及≤60 mg的皮质类固醇起始剂量与良好临床结局相关。
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