Abstract
The association of immune-related adverse events (irAEs) and baseline peripheral blood count ratios with the effectiveness of immune checkpoint inhibitor (ICI) plus chemotherapy in patients with non-small cell lung cancer (NSCLC) remains unclear. This multicenter, retrospective study analyzed data from 191 patients treated with pembrolizumab or atezolizumab plus chemotherapy as first-line therapy across five hospitals in Japan between December 2018 and March 2021. Progression-free survival (PFS) and overall survival (OS) were assessed in relation to irAEs within a 6-week landmark analysis and baseline peripheral blood count ratios using Cox proportional hazards models. IrAEs occurred in 70 patients (36.6%) and showed no substantial association with survival (PFS: hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 0.70–1.53 and OS: HR = 0.82, 95% CI = 0.49–1.34). Conversely, baseline peripheral blood count ratios were considerably linked to survival. A higher neutrophil-to-lymphocyte ratio correlated with reduced PFS (adjusted HR = 1.62, 95% CI = 1.10–2.40) and OS (adjusted HR = 2.50, 95% CI = 1.53–4.09), with similar trends for the lymphocyte-to-monocyte and platelet-to-lymphocyte ratios. Collectively, these findings suggest that although irAEs were not predictive of survival, baseline blood count ratios can serve as prognostic biomarkers in patients with NSCLC receiving chemoimmunotherapy.
Data availability
The data underlying this article cannot be shared publicly to protect the privacy of the individuals who participated in this study. The data will be shared upon a reasonable request to the corresponding author.
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Acknowledgements
We extend our gratitude to all patients and multidisciplinary team staff at the National Hospital Organization Hokkaido Cancer Center, Nagoya City University Hospital, Showa University Hospital, Gifu University Hospital, and Keio University Hospital for their participation in this study. We also thank Prof. Kazunori Kimura, Prof. Tadanori Sasaki, and the Effectiveness of Platinum Chemotherapy and Immune Checkpoint Inhibitors by Concomitant Use (EPIC) investigators for their valuable support. Additionally, we are grateful to Editage (www.editage.com) for the English language editing.
Funding
This research was supported in part by the Research Foundation for Pharmaceutical Sciences in Japan and the JSPS KAKENHI (grant numbers 23K20374 and 25K15015 to R.U.and 22K06776 to H.K.). The funders had no role in the study’s design, data collection, analysis, interpretation, writing of the manuscript, or the decision to submit the manuscript for publication.
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Conception and design: H.K.Provision of study material or patients: Y.K., S.O., S.F., S.K., and J.E.Collection and/or assembly of data: S.T., M.K., S.N., H.I., Y.O., H.H., M.T., and T.O.Data analysis and interpretation: R.U. and H.K.Manuscript writing: S.T., I.N., and H.K.Final approval of manuscript: All authors.
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I.N. reports employment with Flatiron Health, Inc., an independent member of the Roche group, and stock ownership in Roche. R.U. has consulting/advisory relationships with Eisai, Sawai Pharmaceutical, SBI Pharmaceuticals, Daiichi Sankyo, Statcom, Toregem Biopharma, and EPSCorporation and has received honoraria from Janssen Pharmaceutical, SAS Institute Japan, and Nippon Kayaku outside the submitted work. H.I. received personal fees from Astellas, AstraZeneca, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Nippon Kayaku, Ohara, Sawai, Taiho, and Yakult outside the submitted work. S.O. received research funding from Abbvie, Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Pfizer, MSD, Sanofi, Taiho, and Takeda and lecture fees from AstraZeneca, Chugai, MSD, and Takeda outside the submitted work. S.K. received honoraria fees from AstraZeneca, Chugai, Taiho, Kyorin, Daiichi Sankyo, Bristol-Myers Squibb, MSD, and Amgen outside the submitted work. The remaining authors declare no competing and financial interests.
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Takada, S., Nasu, I., Uozumi, R. et al. Association of immune-related adverse events with survival in patients receiving immune checkpoint inhibitor plus chemotherapy for lung cancer. Sci Rep (2026). https://doi.org/10.1038/s41598-026-46185-7
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DOI: https://doi.org/10.1038/s41598-026-46185-7
