Data Sheet 1_Eosinophil is a predictor of severe immune-related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma: a retrospective multicenter cohort study.docx

IntroductionImmune-related adverse events (irAEs) induced by immune checkpoint inhibitors are difficult to predict and can lead to severe events. Although it is important to develop strategies for the early detection of severe irAEs, there is a lack of evidence on irAEs associated with ipilimumab plus nivolumab therapy for metastatic renal cell carcinoma (RCC). Therefore, this study aimed to investigate the association between eosinophil and severe irAEs in patients receiving ipilimumab plus nivolumab therapy for RCC.
MethodsIn this retrospective study, 161 patients receiving ipilimumab plus nivolumab therapy for RCC were divided into three groups based on whether they experienced Results
Although the eosinophil in the baseline samples did not differ between the severe irAE and non-irAE groups (2.8% vs. 2.5%, P = 0.75), regarding the 2-week samples, the eosinophil was significantly higher in the severe irAE group (mean, 6.6% vs. 3.3%; P < 0.05). Multivariate analysis showed that an eosinophil of ≥3.0% was a risk factor for severe irAEs (odds ratio, 6.01). Median progression-free survival (mPFS), mPFS from the start of ipilimumab plus nivolumab therapy to second-line therapy (mPFS2), and median overall survival (mOS) were the shortest in the non-irAE group. Although the mPFS did not differ between the severe and non-severe irAE groups (9.2 vs 14.2 months, P = 0.45), notably, mPFS2 and mOS in the former group tended to be shorter than those in the latter group (mPFS2: 29.2 vs not reached, P = 0.10; mOS: 36.9 vs 52.3 months, P = 0.06).
DiscussionAn increased eosinophil 2 weeks after ipilimumab plus nivolumab therapy may be a predictor of severe irAEs, which are associated with poor prognoses, compared with non-severe irAEs among patients with RCC. We provide a novel rationale for the importance of monitoring eosinophil counts for the early detection of severe irAEs.

研究背景 免疫检查点抑制剂（immune checkpoint inhibitors）诱发的免疫相关不良事件（immune-related adverse events, irAEs）难以预测，且可能引发严重不良事件。尽管开发重症irAEs早期检测策略至关重要，但目前尚缺乏伊匹单抗（ipilimumab）联合纳武利尤单抗（nivolumab）治疗转移性肾细胞癌（renal cell carcinoma, RCC）相关irAEs的循证证据。因此，本研究旨在探讨接受伊匹单抗联合纳武利尤单抗治疗的RCC患者中，嗜酸性粒细胞（eosinophil）与重症irAEs之间的关联。
研究方法 本项回顾性研究（retrospective study）纳入161例接受伊匹单抗联合纳武利尤单抗治疗的RCC患者，根据是否发生[原文疑似格式混淆]分为三组。
研究结果 尽管重症irAEs组与非irAEs组的基线样本（baseline samples）嗜酸性粒细胞占比无显著差异（2.8% vs. 2.5%，P=0.75），但在治疗2周后的样本中，重症irAEs组的嗜酸性粒细胞占比显著升高（均值：6.6% vs. 3.3%；P<0.05）。多因素分析（multivariate analysis）显示，嗜酸性粒细胞占比≥3.0%是重症irAEs的危险因素（比值比：6.01）。非irAEs组的无进展生存期中位值（median progression-free survival, mPFS）、伊匹单抗联合纳武利尤单抗治疗起始至二线治疗（second-line therapy）的mPFS（mPFS2）以及总生存期中位值（median overall survival, mOS）均最短。尽管重症irAEs组与非重症irAEs组的mPFS无显著差异（9.2 vs 14.2个月，P=0.45），但值得注意的是，前者的mPFS2与mOS均短于后者（mPFS2：29.2 vs 未达到，P=0.10；mOS：36.9 vs 52.3个月，P=0.06）。
讨论 与RCC患者中的非重症irAEs相比，伊匹单抗联合纳武利尤单抗治疗2周后嗜酸性粒细胞升高可作为重症irAEs的预测因子，且重症irAEs与不良预后相关。本研究为监测嗜酸性粒细胞计数以早期检测重症irAEs的重要性提供了全新的理论依据。