Elevated eosinophils as predictor of immune-related adverse events after ipilimumab and nivolumab treatment of advanced and metastatic renal cell carcinoma

Abstract

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.

Editorial Comment from Dr. Kato to Elevated eosinophils proportion as predictor of immune‐related adverse events after ipilimumab and nivolumab treatment of advanced and metastatic renal cell carcinoma

“…In the present study, Tasaki et al analyzed the number of peripheral eosinophils from 75 mRCC patients before and 2 weeks after starting nivolumab plus ipilimumab and investigated the detail grade of irAE as well as the number of eosinophils. 3 The authors found that the elevated eosinophil level was likely to be effective biomarker for predicting grade ≥2 irAE onset as evidenced by univariate and multivariate analysis. Interestingly, an increase eosinophil level was observed in many types of irAEs including endocrine, gastrointestinal, pulmonary and skin disorders, prompting physicians for careful monitoring of these patients.…”

“…In the present study, Tasaki et al . analyzed the number of peripheral eosinophils from 75 mRCC patients before and 2 weeks after starting nivolumab plus ipilimumab and investigated the detail grade of irAE as well as the number of eosinophils 3 . The authors found that the elevated eosinophil level was likely to be effective biomarker for predicting grade ≥2 irAE onset as evidenced by univariate and multivariate analysis.…”

Eosinophil may be a predictor of immune‐related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study

“…[16][17][18][19][20] Our previous study showed that increased eosinophil proportion of ≥3.0% is an effective biomarker for predicting irAE occurrences in patients with renal cell carcinoma who received anti-CTLA-4 plus anti-PD-1 combination therapy. 21 In this study, we retrospectively investigated whether the proportion of eosinophils in patients with various cancers treated with different ICIs is a predictor of irAE occurrences.…”