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The prognostic impact of immune-related adverse events in metastatic renal cell carcinoma patients treated with nivolumab: a real-world multi-institutional retrospective study

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Abstract

Background

Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) were correlated with favorable clinical outcome in patients with melanoma. However, in metastatic renal cell carcinoma (mRCC) patients, there have been few reports about the correlation between irAEs and clinical efficacy of anti-programmed cell death protein-1 (PD-1) therapy.

Methods

We retrospectively investigated 160 mRCC patients who started nivolumab monotherapy between September 2016 and July 2019. IrAEs were defined as patients’ AEs having a potential immunological basis that required close follow-up, or immunosuppressive therapy. We compared the data of patients who received nivolumab into two groups based on the occurrence of irAEs and assessed clinical efficacy in both groups.

Results

Of all mRCC patients, 47 patients (29.4%) developed irAEs. In patients who developed irAEs, the objective response rate and disease control rate were 38.8% and 77.6%, which were significantly higher when compared to that in patients without irAEs (p = 0.012 and p < 0.001, respectively). Furthermore, the incidence of irAEs was significantly associated with an increase in progression-free survival (PFS) [Hazard ratio (HR) = 0.4867; p = 0.0006] and overall survival (OS) (HR = 0.526; p = 0.0252). Importantly, PFS and OS seemed to be similar in patients who discontinued treatment because of irAEs and in those who did not discontinue because of irAEs (p = 0.36 and p = 0.35, respectively).

Conclusion

Development of irAEs strongly correlates with clinical benefit for mRCC patients receiving nivolumab monotherapy in real-world settings.

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Abbreviations

ccRCC:

Clear cell renal carcinoma

CTCAE:

Common Terminology Criteria for Adverse Event

DCR:

Disease control rate

ICI:

Immune checkpoint inhibitor

iRAEs:

Immune-related adverse events

mRCC:

Metastatic renal cell carcinoma

ORR:

Objective response rate

OS:

Overall survival

PD-1:

Programmed death 1

PD-L1:

Programmed death-ligand 1

PFS:

Progression-free survival

RCC:

Renal cell carcinoma

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Authors and Affiliations

  1. Department of Urology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Taigo Kato, Koji Hatano, Atsunari Kawashima, Takeshi Ujike, Ryoichi Imamura, Norio Nonomura & Motohide Uemura

  2. Department of Urological Immuno-Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan

    Taigo Kato & Motohide Uemura

  3. Department of Urology, Osaka International Cancer Institute, Chuo-ku, Osaka, 541-8567, Japan

    Akira Nagahara & Kazuo Nishimura

  4. Department of Urology, Osaka General Medical Center, Sumiyoshi-ku, Osaka, 558-8558, Japan

    Norihiko Kawamura, Seiji Yamaguchi & Tetsuya Takao

  5. Departments of Urology, Osaka Rosai Hospital, Sakai, Osaka, 591-8025, Japan

    Wataru Nakata & Masao Tsujihata

  6. Department of Urology, Osaka Police Hospital, Tenoji-ku, Osaka, 543-0035, Japan

    Tetsuji Soda & Shingo Takada

  7. Department of Urology, National Hospital Organization Osaka National Hospital, Chuo-ku, Osaka, 540-0006, Japan

    Kyosuke Matsuzaki & Kensaku Nishimura

Authors
  1. Taigo Kato
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  2. Akira Nagahara
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  3. Norihiko Kawamura
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  4. Wataru Nakata
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  5. Tetsuji Soda
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  6. Kyosuke Matsuzaki
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  7. Koji Hatano
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  8. Atsunari Kawashima
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  9. Takeshi Ujike
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  10. Ryoichi Imamura
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  11. Kensaku Nishimura
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  12. Shingo Takada
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  15. Tetsuya Takao
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  16. Kazuo Nishimura
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  17. Norio Nonomura
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  18. Motohide Uemura
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Contributions

TK was responsible for the study conception and design, and conducted the study, data collection and analysis, drafting the manuscript. AN, NK, WN, TS, KM, KH, AK, TU, RI, KN, SY, TT, MT, ST, KN, NN, and MU conducted the study, data collection and analysis, drafting the manuscript, and manuscript revision. All authors read and approved the final manuscript for submission.

Corresponding author

Correspondence to Taigo Kato.

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Kato, T., Nagahara, A., Kawamura, N. et al. The prognostic impact of immune-related adverse events in metastatic renal cell carcinoma patients treated with nivolumab: a real-world multi-institutional retrospective study. Int J Clin Oncol 26, 954–961 (2021). https://doi.org/10.1007/s10147-021-01872-5

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  • DOI: https://doi.org/10.1007/s10147-021-01872-5

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