Pneumonitis risk from pembrolizumab in non-small cell lung cancer: Interstitial abnormalities matter, and so does treatment.
[BACKGROUND] Immune checkpoint inhibitors (ICIs) such as pembrolizumab have improved outcomes in non-small cell lung cancer (NSCLC), but immune-related pneumonitis remains a clinically important conce
- p-value p = 0.001
- p-value p = 0.059
APA
Yamakawa H, Nakatani D, et al. (2026). Pneumonitis risk from pembrolizumab in non-small cell lung cancer: Interstitial abnormalities matter, and so does treatment.. Respiratory investigation, 64(3), 101421. https://doi.org/10.1016/j.resinv.2026.101421
MLA
Yamakawa H, et al.. "Pneumonitis risk from pembrolizumab in non-small cell lung cancer: Interstitial abnormalities matter, and so does treatment.." Respiratory investigation, vol. 64, no. 3, 2026, pp. 101421.
PMID
41965971
Abstract
[BACKGROUND] Immune checkpoint inhibitors (ICIs) such as pembrolizumab have improved outcomes in non-small cell lung cancer (NSCLC), but immune-related pneumonitis remains a clinically important concern. While interstitial lung disease (ILD) is a known risk factor, the impact of radiologic interstitial lung abnormality (ILA) and host-related factors remains insufficiently understood.
[METHODS] We retrospectively analyzed 236 NSCLC patients treated with pembrolizumab. Patients were categorized by baseline high-resolution computed tomography into ILA, ILD, and non-ILA/ILD groups. Clinical and laboratory parameters, including nutritional and inflammatory indices, were evaluated. Logistic regression and survival analyses were conducted.
[RESULTS] The rates of Grade ≥3 pneumonitis were 20% (ILA), 15% (ILD), and 3% (non-ILA/ILD). ILA was the most significant risk factor (odds ratio [OR] 8.8, p = 0.001), while ILD showed a non-significant trend (OR 5.6, p = 0.059). Notably, approximately 30% of ILD patients were receiving antifibrotics at baseline, and only 1 developed pneumonitis, which was less frequent than in those without antifibrotics. Among patients with ILA or ILD, an elevated neutrophil-to-lymphocyte ratio was the only significant predictor of pneumonitis. Overall survival was shorter in both ILA and ILD groups.
[CONCLUSIONS] Baseline ILA and ILD were both linked to severe ICI-related pneumonitis; the higher risk observed in ILA should be interpreted cautiously, and differences in pre-treatment recognition and management between ILA and established ILD may represent one possible explanation. Based on these findings, close collaboration between ILD-specialists and oncologists is essential for the safe and effective use of ICIs, with careful evaluation and appropriate intervention for both ILA/ILD and lung cancer.
[METHODS] We retrospectively analyzed 236 NSCLC patients treated with pembrolizumab. Patients were categorized by baseline high-resolution computed tomography into ILA, ILD, and non-ILA/ILD groups. Clinical and laboratory parameters, including nutritional and inflammatory indices, were evaluated. Logistic regression and survival analyses were conducted.
[RESULTS] The rates of Grade ≥3 pneumonitis were 20% (ILA), 15% (ILD), and 3% (non-ILA/ILD). ILA was the most significant risk factor (odds ratio [OR] 8.8, p = 0.001), while ILD showed a non-significant trend (OR 5.6, p = 0.059). Notably, approximately 30% of ILD patients were receiving antifibrotics at baseline, and only 1 developed pneumonitis, which was less frequent than in those without antifibrotics. Among patients with ILA or ILD, an elevated neutrophil-to-lymphocyte ratio was the only significant predictor of pneumonitis. Overall survival was shorter in both ILA and ILD groups.
[CONCLUSIONS] Baseline ILA and ILD were both linked to severe ICI-related pneumonitis; the higher risk observed in ILA should be interpreted cautiously, and differences in pre-treatment recognition and management between ILA and established ILD may represent one possible explanation. Based on these findings, close collaboration between ILD-specialists and oncologists is essential for the safe and effective use of ICIs, with careful evaluation and appropriate intervention for both ILA/ILD and lung cancer.