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Systematic surveillance of immune-related adverse events in clinical practice and impact of subsequent steroid medication on survival outcomes

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Abstract

Background

Recent advances in immune-checkpoint inhibitors (ICIs) have highlighted the need for effective management of immune-related adverse events (irAEs). This study aimed to conduct a systematic surveillance of real-world development of irAEs for understanding their characteristics and examine the prognostic impact of steroid use for these events.

Methods

We retrospectively investigated cancer patients treated with ICIs between 2014 and 2021 and collected information about irAEs throughout their development, management, and clinical outcomes.

Results

Overall, 458 patients (45.4%) developed 670 irAEs. The prevalence of irAEs varied by cancer type, but it was increased in regimens with longer treatment durations. Severe irAEs were more common in the nivolumab + ipilimumab and pembrolizumab + axitinib regimens. Patients who received steroids for irAEs at a dosage of < 2 mg/kg had comparable prognosis to those who did not receive steroids; however, patients who received methylprednisolone pulse therapy, primarily for severe pneumonitis and hepatitis, had shorter overall survival than those who did not receive steroids (7.8 versus 23.4 months, p = 0.016). Furthermore, methylprednisolone pulse therapy for irAEs was a poor prognostic factor in multivariate analysis (hazard ratio: 2.19, 95% confidence interval: 1.34–2.86, p < 0.001).

Conclusion

Steroid treatment for irAE does not affect prognosis and should thus be used promptly to control inflammation. However, pulse therapy for severe cases is a poor prognostic factor, and early detection remains the key to managing such irAEs. The irAE characteristics in each regimen should be clarified to establish and provide more sophisticated irAE management, and the current findings will be beneficial to this goal.

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Acknowledgements

We appreciate the physicians and medical workers who managed the ICI and irAEs. We would especially like to thank all the patients involved in this study. This work was partly supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI [grant numbers JP20H01058 to RM] and the Foundation for Promotion of Cancer Research in Japan for RM.

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Authors and Affiliations

  1. Department of Pharmacy, Kyushu University Hospital, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan

    Ryosuke Matsukane, Kimitaka Suetsugu, Kojiro Hata, Keisuke Matsuda, Satoshi Nakao, Haruna Minami, Takeshi Hirota, Nobuaki Egashira & Ichiro Ieiri

  2. Department of Pharmacy, Fukuoka Tokushukai Hospital, 4-5 Sugukita, Kasuga-Shi, Fukuoka, 816-0864, Japan

    Hiroyuki Watanabe

Authors
  1. Ryosuke Matsukane
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  2. Kimitaka Suetsugu
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  3. Kojiro Hata
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  4. Keisuke Matsuda
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  5. Satoshi Nakao
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  6. Haruna Minami
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  7. Hiroyuki Watanabe
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  8. Takeshi Hirota
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  9. Nobuaki Egashira
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  10. Ichiro Ieiri
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Contributions

R.M., K.S. and K.H. conceived and planned the study. R.M., K.M., S.N. and H.M. contributed the retrospective data collection from electric records. R.M. analyzed the data. R.M., K.S., K.H., H.W., T.H., N.E. and I.I. contributed to the interpretation of the results. R.M. took the lead in writing the manuscript. All the authors provided critical feedback and helped shape the research, analysis and manuscript.

Corresponding author

Correspondence to Ichiro Ieiri.

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Matsukane, R., Suetsugu, K., Hata, K. et al. Systematic surveillance of immune-related adverse events in clinical practice and impact of subsequent steroid medication on survival outcomes. Int J Clin Oncol 28, 860–871 (2023). https://doi.org/10.1007/s10147-023-02349-3

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  • DOI: https://doi.org/10.1007/s10147-023-02349-3

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