Pretreatment Lung Function and Checkpoint Inhibitor Pneumonitis in NSCLC

Joshua E Reuss; Emily Brigham; Kevin J Psoter; Khinh Ranh Voong; Bairavi Shankar; David S Ettinger; Kristen A Marrone; Christine L Hann; Benjamin Levy; Josephine L Feliciano; Julie R Brahmer; David Feller-Kopman; Andrew D Lerner; Hans Lee; Lonny Yarmus; Russell K Hales; Franco D'Alessio; Sonye K Danoff; Patrick M Forde; Karthik Suresh; Jarushka Naidoo

doi:10.1016/j.jtocrr.2021.100220

Pretreatment Lung Function and Checkpoint Inhibitor Pneumonitis in NSCLC

JTO Clin Res Rep. 2021 Aug 26;2(10):100220. doi: 10.1016/j.jtocrr.2021.100220. eCollection 2021 Oct.

Authors

Joshua E Reuss^{1

2}, Emily Brigham³, Kevin J Psoter⁴, Khinh Ranh Voong⁵, Bairavi Shankar¹, David S Ettinger¹, Kristen A Marrone^{1

2}, Christine L Hann^{1

2}, Benjamin Levy^{1

2}, Josephine L Feliciano^{1

2}, Julie R Brahmer^{1

2}, David Feller-Kopman³, Andrew D Lerner³, Hans Lee³, Lonny Yarmus³, Russell K Hales⁵, Franco D'Alessio³, Sonye K Danoff³, Patrick M Forde^{1

2}, Karthik Suresh³, Jarushka Naidoo^{1

2}

Affiliations

¹ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
² Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University, Baltimore, Maryland.
³ Division of Pulmonary Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁴ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
⁵ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Abstract

Introduction: Checkpoint inhibitor pneumonitis (CIP) is a serious toxicity of anti-programmed death-(ligand) 1 immunotherapy. Whether pretreatment differences in pulmonary function exist in patients who develop CIP is unknown. We analyzed the pulmonary function tests (PFTs) of patients with NSCLC treated with immune checkpoint inhibitors (ICIs) to evaluate whether pretreatment lung function was associated with CIP development.

Methods: Patients were included if they completed greater than or equal to 1 PFT within 2 years preceding ICI initiation. CIP status (CIP+: developed CIP, CIP-: did not develop CIP) was determined clinically. Generalized estimating equation-based linear regression was used to evaluate the effects of time and CIP on lung function. Primary outcomes included the following: percent-predicted forced expiratory volume in 1 second (FEV1pp), percent-predicted forced vital capacity (FVCpp), and FEV1/FVC.

Results: A total of 43 patients (34 CIP-, 9 CIP+) with 79 PFTs (59 CIP-, 20 CIP+) were included. CIP+ patients had a 21.7% lower pretreatment FEV1pp compared with the CIP- group (95% confidence interval: -38.6 to -4.7). No statistically significant differences in FVCpp or FEV1/FVC were observed. The prevalence of obstructive lung disease was similar in both groups at 67% and 62% for the CIP+ and CIP- cohorts, as was the prevalence of current/former smoking at 100% and 93%, respectively.

Conclusions: Pretherapy differences in lung function were evident between patients who did and did not develop CIP, though the prevalence of obstructive lung disease was similar. Prospective studies are needed to validate these findings, inform potential risk factors for CIP, and investigate the effects of ICI treatment and CIP on pulmonary function in patients with NSCLC.

Keywords: Immune checkpoint inhibitor; Immunotherapy; Non–small cell lung cancer; Pneumonitis; Pulmonary function tests.