Elevated eosinophils as predictor of immune-related adverse events after ipilimumab and nivolumab treatment of advanced and metastatic renal cell carcinoma： a multicenter cohort study Eosinophil could be biomarkers for irAE

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.