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Ipilimumab and nivolumab treatment against advanced and metastatic renal cell carcinoma (RCC) cause 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 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. The median overall and progression-free survival of patients who experienced irAEs (irAE group) were longer than those of the non-irAE group. Grade ≧2 irAEs were associated with poor mPFS. The eosinophil level two weeks after treatment was significantly elevated in the irAEs compared to non-irAE group (mean, 3.0% vs. 5.7%; P < 0.05). The receiver operating characteristic curve revealed the optimal cutoff value for eosinophil levels against ≧grade 2 irAEs two weeks after treatment was 3.0% (area under the curve=0.699). 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). An increased eosinophil level two weeks after treatment might be an effective biomarker for ≧grade 2 irAEs in patients with RCC treated with ipilimumab and nivolumab.

Purpose: 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 irAEs in RCC.Methods: 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 two weeks after treatment, and immediately after irAE development. Median overall (mOS) and progression-free (mPFS) survival were examined by Kaplan–Meier method. The optimal cut-off value for irAE was determined by a receiver operating characteristic (ROC) curve. Univariate and multivariate analyses were undertaken to identify predictors of irAEs.Results: The mOS and mPFS of patients who experienced irAEs (irAE group) were longer than those of the non-irAE group. Grade ≧2 irAEs were associated with poor mPFS. The eosinophil level two weeks after treatment was significantly upregulated in the irAE compared to non-irAE group (mean, 3.0% vs. 5.7%; P < 0.05). The ROC curve revealed the optimal cut-off value for eosinophil levels against ≧grade 2 irAE two weeks after treatment was 3.0% (area under the curve=0.699). In multivariate analyses, an eosinophil level ≧3.0% was a risk factor for ≧grade 2 irAE (odds ratio 4.18, 95% confidence interval 1.16–15.1).Conclusion: An increased eosinophil level two weeks after treatment might be an effective biomarker for irAEs in patients with RCC treated with ipilimumab and nivolumab.