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

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.

• Authors: Daiki Murata, Koichi Azuma, Kenta Murotani, Norikazu Matsuo, Goushi Matama, Takaaki Tokito, Tetsuro Sasada, Tomoaki Hoshino
• Journal: Lung cancer (Amsterdam, Netherlands) (Lung Cancer) Vol. 184 Pg. 107351 (10 2023) ISSN: 1872-8332 [Electronic] Ireland
• PMID: 37639819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• Immune Checkpoint Inhibitors
• Interleukin-6
• Matrix Metalloproteinase 1

Topics

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