Eosinophil is a predictor of severe immune-related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma: a retrospective multicenter cohort study

IntroductionImmune-related adverse events (irAEs) induced by immune checkpoint inhibitors are difficult to predict and can lead to severe events. Although it is important to develop strategies for the early detection of severe irAEs, there is a lack of evidence on irAEs associated with ipilimumab pl...

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Main Authors: Yoshihiko Tasaki, Shuzo Hamamoto, Shimpei Yamashita, Junya Furukawa, Kazutoshi Fujita, Ryotaro Tomida, Makito Miyake, Noriyuki Ito, Hideto Iwamoto, Yoshihisa Mimura, Yosuke Sugiyama, Rei Unno, Atsushi Okada, Takahiro Yasui, Yoko Furukawa-Hibi
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Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483956/full
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author Yoshihiko Tasaki
Shuzo Hamamoto
Shimpei Yamashita
Junya Furukawa
Kazutoshi Fujita
Ryotaro Tomida
Makito Miyake
Noriyuki Ito
Hideto Iwamoto
Yoshihisa Mimura
Yosuke Sugiyama
Rei Unno
Atsushi Okada
Takahiro Yasui
Yoko Furukawa-Hibi
author_facet Yoshihiko Tasaki
Shuzo Hamamoto
Shimpei Yamashita
Junya Furukawa
Kazutoshi Fujita
Ryotaro Tomida
Makito Miyake
Noriyuki Ito
Hideto Iwamoto
Yoshihisa Mimura
Yosuke Sugiyama
Rei Unno
Atsushi Okada
Takahiro Yasui
Yoko Furukawa-Hibi
author_sort Yoshihiko Tasaki
collection DOAJ
description IntroductionImmune-related adverse events (irAEs) induced by immune checkpoint inhibitors are difficult to predict and can lead to severe events. Although it is important to develop strategies for the early detection of severe irAEs, there is a lack of evidence on irAEs associated with ipilimumab plus nivolumab therapy for metastatic renal cell carcinoma (RCC). Therefore, this study aimed to investigate the association between eosinophil and severe irAEs in patients receiving ipilimumab plus nivolumab therapy for RCC.MethodsIn this retrospective study, 161 patients receiving ipilimumab plus nivolumab therapy for RCC were divided into three groups based on whether they experienced <grade 2 irAEs (non-severe irAE group), ≥grade 3 irAEs (severe irAE group), or not (non-irAE group). We examined the proportion of eosinophils before and 2 weeks after treatment (baseline and 2-week samples, respectively).ResultsAlthough the eosinophil in the baseline samples did not differ between the severe irAE and non-irAE groups (2.8% vs. 2.5%, P = 0.75), regarding the 2-week samples, the eosinophil was significantly higher in the severe irAE group (mean, 6.6% vs. 3.3%; P < 0.05). Multivariate analysis showed that an eosinophil of ≥3.0% was a risk factor for severe irAEs (odds ratio, 6.01). Median progression-free survival (mPFS), mPFS from the start of ipilimumab plus nivolumab therapy to second-line therapy (mPFS2), and median overall survival (mOS) were the shortest in the non-irAE group. Although the mPFS did not differ between the severe and non-severe irAE groups (9.2 vs 14.2 months, P = 0.45), notably, mPFS2 and mOS in the former group tended to be shorter than those in the latter group (mPFS2: 29.2 vs not reached, P = 0.10; mOS: 36.9 vs 52.3 months, P = 0.06).DiscussionAn increased eosinophil 2 weeks after ipilimumab plus nivolumab therapy may be a predictor of severe irAEs, which are associated with poor prognoses, compared with non-severe irAEs among patients with RCC. We provide a novel rationale for the importance of monitoring eosinophil counts for the early detection of severe irAEs.
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spelling doaj-art-2e5a6fe006c447feaaea2dbe6ed296f92025-01-09T06:10:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14839561483956Eosinophil is a predictor of severe immune-related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma: a retrospective multicenter cohort studyYoshihiko Tasaki0Shuzo Hamamoto1Shimpei Yamashita2Junya Furukawa3Kazutoshi Fujita4Ryotaro Tomida5Makito Miyake6Noriyuki Ito7Hideto Iwamoto8Yoshihisa Mimura9Yosuke Sugiyama10Rei Unno11Atsushi Okada12Takahiro Yasui13Yoko Furukawa-Hibi14Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanDepartment of Urology, Wakayama Medical University, Wakayama, JapanDepartment of Urology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, JapanDepartment of Urology, Kindai University Faculty of Medicine, Osaka, JapanDepartment of Urology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, JapanDepartment of Urology, Nara Medical University, Nara, JapanDepartment of Urology, Japanese Red Cross Wakayama Medical Center, Wakayama, JapanDivision of Urology, Department of Surgery, Tottori University Faculty of Medicine Graduate School of Medicine, Tottori, JapanDepartment of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanDepartment of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanDepartment of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanDepartment of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, JapanIntroductionImmune-related adverse events (irAEs) induced by immune checkpoint inhibitors are difficult to predict and can lead to severe events. Although it is important to develop strategies for the early detection of severe irAEs, there is a lack of evidence on irAEs associated with ipilimumab plus nivolumab therapy for metastatic renal cell carcinoma (RCC). Therefore, this study aimed to investigate the association between eosinophil and severe irAEs in patients receiving ipilimumab plus nivolumab therapy for RCC.MethodsIn this retrospective study, 161 patients receiving ipilimumab plus nivolumab therapy for RCC were divided into three groups based on whether they experienced <grade 2 irAEs (non-severe irAE group), ≥grade 3 irAEs (severe irAE group), or not (non-irAE group). We examined the proportion of eosinophils before and 2 weeks after treatment (baseline and 2-week samples, respectively).ResultsAlthough the eosinophil in the baseline samples did not differ between the severe irAE and non-irAE groups (2.8% vs. 2.5%, P = 0.75), regarding the 2-week samples, the eosinophil was significantly higher in the severe irAE group (mean, 6.6% vs. 3.3%; P < 0.05). Multivariate analysis showed that an eosinophil of ≥3.0% was a risk factor for severe irAEs (odds ratio, 6.01). Median progression-free survival (mPFS), mPFS from the start of ipilimumab plus nivolumab therapy to second-line therapy (mPFS2), and median overall survival (mOS) were the shortest in the non-irAE group. Although the mPFS did not differ between the severe and non-severe irAE groups (9.2 vs 14.2 months, P = 0.45), notably, mPFS2 and mOS in the former group tended to be shorter than those in the latter group (mPFS2: 29.2 vs not reached, P = 0.10; mOS: 36.9 vs 52.3 months, P = 0.06).DiscussionAn increased eosinophil 2 weeks after ipilimumab plus nivolumab therapy may be a predictor of severe irAEs, which are associated with poor prognoses, compared with non-severe irAEs among patients with RCC. We provide a novel rationale for the importance of monitoring eosinophil counts for the early detection of severe irAEs.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483956/fulleosinophilipilimumabnivolumabimmune-related adverse eventrenal cell carcinoma
spellingShingle Yoshihiko Tasaki
Shuzo Hamamoto
Shimpei Yamashita
Junya Furukawa
Kazutoshi Fujita
Ryotaro Tomida
Makito Miyake
Noriyuki Ito
Hideto Iwamoto
Yoshihisa Mimura
Yosuke Sugiyama
Rei Unno
Atsushi Okada
Takahiro Yasui
Yoko Furukawa-Hibi
Eosinophil is a predictor of severe immune-related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma: a retrospective multicenter cohort study
Frontiers in Immunology
eosinophil
ipilimumab
nivolumab
immune-related adverse event
renal cell carcinoma
title Eosinophil is a predictor of severe immune-related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma: a retrospective multicenter cohort study
title_full Eosinophil is a predictor of severe immune-related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma: a retrospective multicenter cohort study
title_fullStr Eosinophil is a predictor of severe immune-related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma: a retrospective multicenter cohort study
title_full_unstemmed Eosinophil is a predictor of severe immune-related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma: a retrospective multicenter cohort study
title_short Eosinophil is a predictor of severe immune-related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma: a retrospective multicenter cohort study
title_sort eosinophil is a predictor of severe immune related adverse events induced by ipilimumab plus nivolumab therapy in patients with renal cell carcinoma a retrospective multicenter cohort study
topic eosinophil
ipilimumab
nivolumab
immune-related adverse event
renal cell carcinoma
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1483956/full
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