Impact of Organ-Specific Severe Immune-Related Adverse Events on Long-Term Survival and Treatment Transitions in Metastatic Renal Cell Carcinoma: A 5-Year Multicenter Multistate Analysis.
8 affiliations
- 1Department of Clinical Pharmaceutics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
- 2Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
- 3Department of Urology, Kainan Hospital, Yatomi, Aichi, Japan.
- 4Department of Urology, Anjo Kosei Hospital, Anjo, Aichi, Japan.
- 5Department of Urology, Toyota Kosei Hospital, Toyota, Aichi, Japan.
- 6Department of Urology, Konan Kosei Hospital, Konan, Aichi, Japan.
- 7Department of Urology, Nagoya Tokushukai General Hospital, Kasugai, Aichi, Japan.
- 8Department of Urology, Gamagori City General Hospital, Gamagori, Aichi, Japan.
Abstract
Introduction
Immune-related adverse events (irAEs) frequently occur during combination immune checkpoint inhibition. However, their prognostic impact may vary according to organ involvement and severity. In this study, we exploratorily evaluated whether severe non-endocrine irAEs represent a temporally distinct and prognostically unfavorable clinical phenotype in patients with metastatic renal cell carcinoma (mRCC) treated with ipilimumab plus nivolumab.Patients and methods
We analyzed 63 patients with mRCC treated with ipilimumab plus nivolumab who were followed for at least 5 years. Patients were categorized into non-irAE, non-severe + severe endocrine irAE, and severe non-endocrine irAE groups. Overall survival (OS) was assessed. Multistate modeling was used to evaluate the transitions between treatment, irAE occurrence, and death. Landmark analyses were performed at 8 and 12 weeks to address immortal time bias.Results
The severe non-endocrine irAE group was associated with inferior OS. The multistate analysis revealed a potentially increased risk of direct transition from ipilimumab plus nivolumab to death in the severe non-endocrine irAE group. A significantly higher proportion of patients in the severe non-endocrine irAE group experienced irAEs within 30 days. No significant association was observed in the 8- and 12-week landmark analyses.Conclusion
In this exploratory retrospective study, severe non-endocrine irAEs showed an association with early onset and potentially unfavorable clinical outcomes in patients with mRCC receiving ipilimumab plus nivolumab. Given the limited sample size, these findings should be interpreted cautiously and require confirmation in larger independent cohorts.
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BibTeX
@article{tasaki2026impact,
title = {{Impact of Organ-Specific Severe Immune-Related Adverse Events on Long-Term Survival and Treatment Transitions in Metastatic Renal Cell Carcinoma: A 5-Year Multicenter Multistate Analysis.}},
author = {Yoshihiko Tasaki and Kazumasa Sato and Shuzo Hamamoto and Yosuke Sugiyama and Hiroaki Ikoma and Kengo Kawase and Hiroko Suzuki and Yusuke Noda and Masayuki Usami and Yohei Tsubouchi and Ryuga Kato and Takuya Sakata and Misato Tomita and Yoshihisa Mimura and Takashi Nagai and Rei Unno and Toshiki Etani and Taku Naiki and Takahiro Yasui and Yoko Furukawa-Hibi},
journal = {Cancer medicine},
year = {2026},
month = oct,
doi = {10.1002/cam4.72410},
url = {https://europepmc.org/article/MED/42897107},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Impact of Organ-Specific Severe Immune-Related Adverse Events on Long-Term Survival and Treatment Transitions in Metastatic Renal Cell Carcinoma: A 5-Year Multicenter Multistate Analysis.
AU - Yoshihiko Tasaki
AU - Kazumasa Sato
AU - Shuzo Hamamoto
AU - Yosuke Sugiyama
AU - Hiroaki Ikoma
AU - Kengo Kawase
AU - Hiroko Suzuki
AU - Yusuke Noda
AU - Masayuki Usami
AU - Yohei Tsubouchi
AU - Ryuga Kato
AU - Takuya Sakata
AU - Misato Tomita
AU - Yoshihisa Mimura
AU - Takashi Nagai
AU - Rei Unno
AU - Toshiki Etani
AU - Taku Naiki
AU - Takahiro Yasui
AU - Yoko Furukawa-Hibi
PY - 2026
DA - 2026/10/01
JO - Cancer medicine
DO - 10.1002/cam4.72410
UR - https://europepmc.org/article/MED/42897107
AB - Introduction Immune-related adverse events (irAEs) frequently occur during combination immune checkpoint inhibition. However, their prognostic impact may vary according to organ involvement and severity. In this study, we exploratorily evaluated whether severe non-endocrine irAEs represent a temporally distinct and prognostically unfavorable clinical phenotype in patients with metastatic renal cell carcinoma (mRCC) treated with ipilimumab plus nivolumab.Patients and methods We analyzed 63 patients with mRCC treated with ipilimumab plus nivolumab who were followed for at least 5 years. Patients were categorized into non-irAE, non-severe + severe endocrine irAE, and severe non-endocrine irAE groups. Overall survival (OS) was assessed. Multistate modeling was used to evaluate the transitions between treatment, irAE occurrence, and death. Landmark analyses were performed at 8 and 12 weeks to address immortal time bias.Results The severe non-endocrine irAE group was associated with inferior OS. The multistate analysis revealed a potentially increased risk of direct transition from ipilimumab plus nivolumab to death in the severe non-endocrine irAE group. A significantly higher proportion of patients in the severe non-endocrine irAE group experienced irAEs within 30 days. No significant association was observed in the 8- and 12-week landmark analyses.Conclusion In this exploratory retrospective study, severe non-endocrine irAEs showed an association with early onset and potentially unfavorable clinical outcomes in patients with mRCC receiving ipilimumab plus nivolumab. Given the limited sample size, these findings should be interpreted cautiously and require confirmation in larger independent cohorts.
SN - 2045-7634
ER -