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Multicenter Study
. 2025 Jul 25;15(1):27163.
doi: 10.1038/s41598-025-08767-9.

Eosinophils as a predictive marker of treatment-related adverse events in mRCC patients treated with first-line immune-checkpoint inhibitor combination therapy

Tatsushi Kawada  1 , Satoshi Katayama  1 , Takafumi Yanagisawa  2 , Keiichiro Mori  2 , Wataru Fukuokaya  2 , Kazumasa Komura  3 , Takuya Tsujino  3 , Ryoichi Maenosono  3 , Kiyoshi Takahara  4 , Takuhisa Nukaya  4 , Lan Inoki  5 , Shingo Toyoda  5 , Takeshi Hashimoto  6 , Yosuke Hirasawa  6 , Kohei Edamura  1 , Tomoko Kobayashi  1 , Kensuke Bekku  1 , Shingo Nishimura  1 , Takehiro Iwata  1 , Takuya Sadahira  1 , Yusuke Tominaga  1 , Tomoaki Yamanoi  1 , Kasumi Yoshinaga  1 , Kazuma Tsuboi  1 , Yasuyuki Kobayashi  1 , Atsushi Takamoto  1 , Kyohei Kurose  1 , Takahiro Kimura  2 , Haruhito Azuma  3 , Ryoichi Shiroki  4 , Kazutoshi Fujita  5 , Yoshio Ohno  6 , Motoo Araki  7 ; JK-FOOT study group
Affiliations
Multicenter Study

Eosinophils as a predictive marker of treatment-related adverse events in mRCC patients treated with first-line immune-checkpoint inhibitor combination therapy

Tatsushi Kawada et al. Sci Rep. .

Abstract

Immune checkpoint inhibitors (ICIs) are a key component of first-line treatment for metastatic renal cell carcinoma (mRCC). However, predicting treatment-related adverse events (TRAEs) remains challenging. This study investigated the utility of eosinophil-related biomarkers as predictors of Common Terminology Criteria for Adverse Events grade ≥ 3 TRAEs in mRCC patients undergoing ICI combination therapy. In this retrospective analysis across 21 hospitals in Japan, we examined 180 patients treated with ICI/ICI therapy and 216 patients treated with ICI/tyrosine kinase inhibitor (TKI) therapy. Grade ≥ 3 TRAEs occurred in 39.4% and 31.9% of patients in the ICI/ICI and ICI/TKI groups, respectively. An elevated eosinophil proportion of ≥ 2.0% (odds ratio [OR]: 2.36; 95% CI [confidence interval] 1.23-4.54, p = 0.01) and a low neutrophil/eosinophil ratio (NER) of ≤ 40.0 (OR: 2.78, 95% CI 1.39-5.53, p = 0.004) were significant predictors of severe TRAEs in the ICI/ICI group. However, no significant associations were found in the ICI/TKI group. These findings may help identify patients who suffer from grade ≥ 3 TRAEs and help determine individualized treatment strategies in patients with mRCC.

Keywords: Eosinophil; ICI; Immune checkpoint inhibitor; Immune-related adverse event; Renal cell carcinoma; Treatment-related adverse event.

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Conflict of interest statement

Declarations. Competing interests: Kazutoshi Fujita received honorarium from Ono, Bristle, MSD, Eisai, Pfizer, Merk, and Takeda. Takahiro Kimura is a paid consultant/advisor of Astellas, Bayer, Janssen, Sanofi and Takeda. The other authors declare no conflicts of interest associated with this manuscript. Ethical approval: This study was approved by the ethical review board at Osaka Medical and Pharmaceutical University; approval number: RIN–750–2571 executed in accordance with the principles outlined in the World Medical Association Declaration of Helsinki, with the participants’ informed consent.

Figures

Fig. 1
Fig. 1
Flow chart of the patient selection process.
See this image and copyright information in PMC

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