Survival and soluble immune mediators of immune checkpoint inhibitor-induced interstitial lung disease in patients with non-small cell lung cancer

Daiki Murata; Koichi Azuma; Kenta Murotani; Norikazu Matsuo; Goushi Matama; Takaaki Tokito; Tetsuro Sasada; Tomoaki Hoshino

doi:10.1016/j.lungcan.2023.107351

Survival and soluble immune mediators of immune checkpoint inhibitor-induced interstitial lung disease in patients with non-small cell lung cancer

Lung Cancer. 2023 Oct:184:107351. doi: 10.1016/j.lungcan.2023.107351. Epub 2023 Aug 20.

Authors

Daiki Murata¹, Koichi Azuma², Kenta Murotani³, Norikazu Matsuo¹, Goushi Matama¹, Takaaki Tokito¹, Tetsuro Sasada⁴, Tomoaki Hoshino¹

Affiliations

¹ Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
² Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan. Electronic address: azuma@med.kurume-u.ac.jp.
³ Biostatistics Center, Kurume University School of Medicine, Fukuoka, Japan.
⁴ Cancer Vaccine and Immunotherapy Center and Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Kanagawa, Japan.

PMID: 37639819
DOI: 10.1016/j.lungcan.2023.107351

Abstract

Background: Immune checkpoint inhibitor-related interstitial lung disease (ICI-ILD) is a serious adverse event frequently observed in patients with non-small cell lung cancer (NSCLC). We investigated the clinical effects and mechanism of action of ICI-ILD in NSCLC patients treated with ICI.

Methods: We retrospectively screened patients with advanced or recurrent NSCLC who received PD-1/PD-L1 inhibitor monotherapy and examined the prognostic impact of ICI-ILD. In addition, we analyzed the levels of 72 different soluble immune mediators in pre-treatment plasma to explore possible mechanisms associated with the development of ICI-ILD. Furthermore, the relationships between soluble immune mediators associated with ICI-ILD development and survival were analyzed.

Results: Of 141 patients with NSCLC, 25 (17.7%) developed ICI-ILD. Logistic regression analysis revealed that pre-treatment CXCL9, MMP-1, IL-6, and IL-19 levels were associated with ICI-ILD development. There were no significant differences in progression-free survival (PFS) and overall survival (OS) between patients with or without ICI-ILD. In patients with ICI-ILD, patients with lower grade ICI-ILD had better OS than those with higher-grade ICI-ILD. In ICI-ILD patients, there was a trend for patients with lower-grade ICI-ILD to have better PFS and OS than those with higher-grade ICI-ILD. Among four soluble immune mediators associated with ICI-ILD, a high level of IL-19 was significantly correlated with worse OS and PFS.

Conclusion: The identified soluble immune mediators, including CXCL9, MMP-1, IL-6, and IL-19, may be useful as biomarkers to associate with ICI-ILD development. Although we did not detect significant differences in PFS and OS between patients with and without ICI-ILD, PFS and OS were longer in those with lower-grade ICI-ILD than in patients with higher-grade ICI-ILD. Among biomarkers, IL-19 may be a causal and prognostic factor for ICI-ILD.

Keywords: Chemokine; Cytokine; Immune checkpoint inhibitor; Interstitial lung disease; NSCLC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Non-Small-Cell Lung* / drug therapy
Humans
Immune Checkpoint Inhibitors / adverse effects
Interleukin-6
Lung Diseases, Interstitial* / etiology
Lung Neoplasms* / drug therapy
Matrix Metalloproteinase 1
Neoplasm Recurrence, Local
Retrospective Studies

Substances

Immune Checkpoint Inhibitors
Interleukin-6
Matrix Metalloproteinase 1