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Association between pre-treatment chest imaging and pulmonary function abnormalities and immune checkpoint inhibitor pneumonitis

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A Correction to this article was published on 18 February 2023

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Abstract

Background

Immune checkpoint inhibitors (ICIs) are a first-line treatment for various metastatic solid tumors. Pneumonitis is a potentially devastating complication of ICI treatment and a leading cause of ICI-related mortality. Here, we evaluate whether abnormal pre-treatment pulmonary function tests (PFTs) or interstitial abnormalities on computed tomography of the chest (CT chest) prior to ICI are associated with the development of ICI-pneumonitis (ICI-p).

Methods

We conducted a retrospective cohort study of consecutive patients who received at least one dose of ICI from 2011 to 2017 at The Ohio State University. Potential risk factors for ICI-p, including abnormal PFTs and CT chest, were recorded. These risk factors were compared between patients with and without pneumonitis.

Results

In total, 1097 patients were included, 46 with ICI-p and 1051 without. Ninety percent of patients had pre-treatment chest imaging, while only 10% had pre-treatment PFTs. On multivariable analysis, interstitial abnormalities and reduced total lung capacity (TLC) were significantly associated with development of ICI-p (hazard ratio of 42.42 [95% CI; 15.04–119.67] and hazard ratio of 4.04 [95% CI; 1.32–12.37]), respectively. No other PFT abnormality was associated with increased risk of ICI-p. There was no significant difference in overall survival in patients who did or did not develop ICI-p (p = 0.332).

Conclusions

Pre-existing interstitial abnormalities on CT chest and reduced TLC were strongly associated with develo** ICI-p. Prospective studies are warranted to further explore the role of PFTs as a potential tool for identifying patients at highest risk for develo** ICI-p.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by the National Institutes of Health (P30CA016058). Research support provided by the REDCap project and The Ohio State University Center for Clinical and Translational Science grant support (National Center for Advancing Translational Sciences, Grant UL1TR002733). Dr. Owen is supported by the LUNGevity Foundation Career Development Award. Dr. Presley is supported by the National Institute of Aging (C.J.P., 1K76AG074923-01) the following provide research funding to the Institution: BMS, Genentech, Pfizer, AbbVie, Merck, Elevation Oncology, Onc.ai.

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Author notes

  1. Dwight H. Owen and Kevin Ho have equally contributed to this work.

Authors and Affiliations

  1. Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Alex Wong & Maria Riley

  2. Center for Biostatistics, The Ohio State University – James Comprehensive Cancer Center, Columbus, OH, USA

    Songzhu Zhao & Lai Wei

  3. Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, 241 W 11th Ave, Suite 5000, Columbus, OH, 43201, USA

    **g Gennie Wang, Vince Esguerra & Dwight H. Owen

  4. Division of Medical Oncology, Department of Internal Medicine, The Ohio State University – James Comprehensive Cancer Center, Columbus, OH, USA

    Mingjia Li, Gabrielle Lopez, Gregory A. Otterson, Kari Kendra, Carolyn J. Presley & Kevin Ho

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Contributions

Material preparation, data collection, data analysis, and manuscript preparation were performed by AW, MR, DO, and KH. Database building and data collection were done by ML, GL, GO, KK, and CP. Statistical analysis was performed by SZ and LW. Imaging review was done by VE and JW. All authors reviewed the manuscript and approved the final submission.

Corresponding author

Correspondence to Kevin Ho.

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Conflict of interests

Dr. Otterson serves as a consultant on the Data Safety Monitoring Board on Beigene and Novocure. The remaining authors have no relevant financial or non-financial interests to disclose.

Ethics approval

The study protocol was reviewed and approved by the Ohio State Institutional Review Board (2016C0070), and a waiver of informed consent was granted due to the retrospective nature of the study.

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Wong, A., Riley, M., Zhao, S. et al. Association between pre-treatment chest imaging and pulmonary function abnormalities and immune checkpoint inhibitor pneumonitis. Cancer Immunol Immunother 72, 1727–1735 (2023). https://doi.org/10.1007/s00262-023-03373-y

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