Risk Factors for Pneumonitis in Patients with Unresectable Advanced Non-small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors
Abstract
Objective Immune checkpoint inhibitors (ICIs) have become a standard treatment for various cancers; however, they can sometimes induce immune-related adverse events (irAEs). Although pneumonitis during ICI therapy is a critical irAE, the risk factors for pneumonitis remain unclear. This study aimed to evaluate the predictive factors for pneumonitis in patients with non-small cell lung cancer (NSCLC) treated with ICIs. Methods We conducted a retrospective study of 403 patients with unresectable advanced NSCLC who underwent immune checkpoint inhibitor therapy between January 1, 2016, and January 31, 2024. Results Among these 403 patients, pneumonitis occurred in 64 (15.9%), including grade ≥3 pneumonitis in 13 (3.2%). The cumulative incidence of pneumonitis differed significantly according to the presence of pre-existing pulmonary disease and was highest in patients with pre-existing idiopathic interstitial pneumonia (IIP). All three cases of grade 5 pneumonitis occurred in patients with IIP without a honeycomb lung. In a multivariate Fine-Gray analysis, pre-existing IIP was independently associated with pneumonitis, whereas honeycomb lung was not associated with pneumonitis development or severity. Conclusion Pre-existing IIP was independently associated with pneumonitis during immune checkpoint inhibitor therapy. Therefore, baseline lung involvement, particularly pre-existing IIP, should be carefully evaluated before initiating immune checkpoint inhibitor therapy.
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BibTeX
@article{isono2026risk,
title = {{Risk Factors for Pneumonitis in Patients with Unresectable Advanced Non-small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors}},
author = {Taisuke Isono and Akihiro Ishida and Yoko Onodera and Ayaka Kojima and Kyuto Odajima and Takashi Nishida and Yoichi Kobayashi and Takashi Ishiguro and Yotaro Takaku and Kazuyoshi Kurashima and Naho Kagiyama},
journal = {Internal Medicine},
year = {2026},
month = nov,
doi = {10.2169/internalmedicine.6374-25},
url = {https://www.jstage.jst.go.jp/article/internalmedicine/65/21/65_6374-25/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Risk Factors for Pneumonitis in Patients with Unresectable Advanced Non-small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors
AU - Taisuke Isono
AU - Akihiro Ishida
AU - Yoko Onodera
AU - Ayaka Kojima
AU - Kyuto Odajima
AU - Takashi Nishida
AU - Yoichi Kobayashi
AU - Takashi Ishiguro
AU - Yotaro Takaku
AU - Kazuyoshi Kurashima
AU - Naho Kagiyama
PY - 2026
DA - 2026/11/01
JO - Internal Medicine
DO - 10.2169/internalmedicine.6374-25
UR - https://www.jstage.jst.go.jp/article/internalmedicine/65/21/65_6374-25/_article
AB - Objective Immune checkpoint inhibitors (ICIs) have become a standard treatment for various cancers; however, they can sometimes induce immune-related adverse events (irAEs). Although pneumonitis during ICI therapy is a critical irAE, the risk factors for pneumonitis remain unclear. This study aimed to evaluate the predictive factors for pneumonitis in patients with non-small cell lung cancer (NSCLC) treated with ICIs. Methods We conducted a retrospective study of 403 patients with unresectable advanced NSCLC who underwent immune checkpoint inhibitor therapy between January 1, 2016, and January 31, 2024. Results Among these 403 patients, pneumonitis occurred in 64 (15.9%), including grade ≥3 pneumonitis in 13 (3.2%). The cumulative incidence of pneumonitis differed significantly according to the presence of pre-existing pulmonary disease and was highest in patients with pre-existing idiopathic interstitial pneumonia (IIP). All three cases of grade 5 pneumonitis occurred in patients with IIP without a honeycomb lung. In a multivariate Fine-Gray analysis, pre-existing IIP was independently associated with pneumonitis, whereas honeycomb lung was not associated with pneumonitis development or severity. Conclusion Pre-existing IIP was independently associated with pneumonitis during immune checkpoint inhibitor therapy. Therefore, baseline lung involvement, particularly pre-existing IIP, should be carefully evaluated before initiating immune checkpoint inhibitor therapy.
SN - 1349-7235
SN - 0918-2918
ER -