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Risk of pneumonitis in non-small cell lung cancer patients with preexisting interstitial lung diseases treated with immune checkpoint inhibitors: a nationwide retrospective cohort study

Abstract

Background

Chemotherapy for non-small cell lung cancer (NSCLC) patients with preexisting interstitial lung diseases (ILDs) increases the risk of developing pneumonitis. However, the association between pneumonitis and immune checkpoint inhibitors (ICIs) and related factors remains unclear.

Methods

We conducted a retrospective cohort study using a nationwide inpatient database. We included patients (aged ≥ 20 years) newly diagnosed with ILD and NSCLC and who started chemotherapy (ICIs or conventional chemotherapy) between January 2016 and December 2019. The primary endpoint was the onset of pneumonitis. We estimated the cumulative incidence function of pneumonitis and compared it with patients taking ICIs and patients receiving conventional chemotherapy using Gray’s test. We calculated the subdistribution hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of pneumonitis using Fine and Gray’s model to adjust for sex, age, smoking status, histology of NSCLC, surgical history, and medical histories, considering death as the competing risk.

Results

We identified 1177 patients (mean age 72 years, 13.8% female), of which 328 and 849 were in the ICI and conventional chemotherapy groups, respectively. There was no significant difference in the cumulative incidence function of pneumonitis between the two groups (p = 0.868). The adjusted subdistribution HR for the incidence of pneumonitis was 1.08 (95% CI: 0.74–1.57). Age (≥ 65 years) (HR: 1.86, 95% CI: 1.11–3.10) and smoking history (HR: 2.04, 95% CI: 1.02–4.11) were associated with developing pneumonitis.

Conclusion

The risk of developing pneumonitis with ICIs for NSCLC patients with preexisting ILD was similar to that with conventional chemotherapy.

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Acknowledgements

We would like to thank Editage (http://www.editage.com) for English-language editing of this manuscript.

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Authors and Affiliations

Authors

Contributions

KS designed the study, performed the analysis (and took responsibility for data integrity and accuracy), discussed the results, and drafted the manuscript. IS designed the study, performed the analysis, discussed the results, and drafted the manuscript. MT designed the study, discussed the results, and drafted the manuscript. KK directed the project, obtained funding and accessible source data, designed the study, discussed the results, and drafted the manuscript. All authors contributed to revisions of the manuscript for critically important content and approved this version of the manuscript.

Corresponding author

Correspondence to Koji Kawakami.

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Conflict of interest

K. Sawa receives payment for lectures from Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. I. Sato holds stack in Astellas Pharma Inc. and Daiichi Sankyo Co., Ltd.M. Takeuchi received a consultation fee from Eisai Co., Ltd. K. Kawakami received advisory fees from Shin Nippon Biomedical Laboratories, Ltd., JMDC Inc., Leber Inc. Kaken Pharmaceutical Co.,Ltd., and Advanced Medical Care Inc.; payment for lectures including service on speakers bureaus from Mitsubishi Corp., Mitsubishi Chemical Holdings Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Kyoto University Original Co., Ltd., McKinsey & Co. Inc., Nikkei Business Publications, Inc., Astellas Pharma Inc., AstraZeneca K.K., Mitsubishi Tanabe Pharma Corp., and IQVIA Services Japan K.K.; research funds from Sumitomo Dainippon Pharma Co., Ltd., Pfizer Inc., Stella Pharma Corporation, CMIC Co., Ltd., Suntory Beverage & Food Ltd., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Mitsubishi Corp. Ltd. and Real World Data, Co., Ltd.; and holds stock in Real World Data, Co., Ltd.

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Sawa, K., Sato, I., Takeuchi, M. et al. Risk of pneumonitis in non-small cell lung cancer patients with preexisting interstitial lung diseases treated with immune checkpoint inhibitors: a nationwide retrospective cohort study. Cancer Immunol Immunother 72, 591–598 (2023). https://doi.org/10.1007/s00262-022-03281-7

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Keywords

  • Immune checkpoint inhibitor
  • Pneumonitis
  • Non-small cell lung cancer
  • Interstitial lung disease