Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Aichi, Nagoya, Japan.
Int J Urol. 2023 Oct;30(10):866-874. doi: 10.1111/iju.15220. Epub 2023 Jun 6.
Ipilimumab and nivolumab treatment against advanced and metastatic renal cell carcinoma (RCC) causes severe and lethal immune-related adverse events (irAEs). Predicting irAEs might improve clinical outcomes, however no practical biomarkers exist. This study examined whether eosinophils could be effective biomarkers for ≥grade 2 irAEs in RCC.
We retrospectively analyzed 75 patients with RCC treated with ipilimumab and nivolumab between August 2018 and March 2021 in a multicenter study. Eosinophils were examined before and 2 weeks after treatment, and immediately after irAEs development. The optimal cut-off value for ≥grade 2 irAEs was determined by a receiver operating characteristic (ROC) curve. Univariate and multivariate analyses were undertaken to identify predictors of ≥grade 2 irAEs.
Two weeks after treatment, eosinophils were significantly upregulated in patients who had experienced ≥grade 2 irAEs than in those who had not experienced irAEs (mean, 5.7% vs. 3.2%; p < 0.05). The optimal cut-off value for eosinophils against ≥grade 2 irAEs was 3.0% (area under the curve = 0.69). In multivariate analyses, an eosinophil level ≥ 3.0% was a risk factor for ≥grade 2 irAEs (odds ratio 4.18, 95% confidence interval 1.16-15.1). The eosinophil level 2 weeks after treatment was upregulated by the onset of any type of irAEs including endocrine, gastrointestinal, pulmonary and skin disorders.
An increased eosinophil level 2 weeks after treatment might be an effective biomarker for ≥grade 2 irAEs in patients with RCC treated with ipilimumab and nivolumab.
依匹单抗和纳武利尤单抗治疗晚期和转移性肾细胞癌（RCC）会引起严重和致命的免疫相关不良事件（irAEs）。预测 irAEs 可能改善临床结局，但目前尚无实用的生物标志物。本研究探讨了嗜酸性粒细胞是否可以作为 RCC 患者发生≥2 级 irAEs 的有效生物标志物。
我们回顾性分析了 2018 年 8 月至 2021 年 3 月间在多中心研究中接受依匹单抗和纳武利尤单抗治疗的 75 例 RCC 患者。在治疗前和治疗后 2 周以及 irAEs 发生后立即检查嗜酸性粒细胞。通过受试者工作特征（ROC）曲线确定用于≥2 级 irAEs 的最佳截断值。采用单因素和多因素分析来确定≥2 级 irAEs 的预测因素。
与未发生 irAEs 的患者相比，发生≥2 级 irAEs 的患者治疗后 2 周时嗜酸性粒细胞显著升高（平均值，5.7%比 3.2%；p<0.05）。嗜酸性粒细胞水平≥3.0%用于预测≥2 级 irAEs 的最佳截断值（曲线下面积=0.69）。多因素分析显示，嗜酸性粒细胞水平≥3.0%是发生≥2 级 irAEs 的危险因素（比值比 4.18，95%置信区间 1.16-15.1）。治疗后 2 周时，嗜酸性粒细胞水平升高与内分泌、胃肠道、肺部和皮肤疾病等任何类型的 irAEs 的发生相关。
治疗后 2 周时嗜酸性粒细胞水平升高可能是预测接受依匹单抗和纳武利尤单抗治疗的 RCC 患者发生≥2 级 irAEs 的有效生物标志物。
Zotero 插件