Risk factors for checkpoint inhibitor pneumonitis in lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

BackgroundImmune checkpoint inhibitors (ICIs) significantly improve survival in lung cancer patients. However, checkpoint inhibitor pneumonitis (CIP) remains a critical safety concern. This meta-analysis systematically evaluates demographic, clinical, and laboratory risk factors associated with CIP...

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Main Authors: Xiaoqing Zhou, Yingnan Xu, Yuanyuan Ying, Ruilin Chen, Zhen Wang, Xin Lv
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1607170/full
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author Xiaoqing Zhou
Xiaoqing Zhou
Yingnan Xu
Yuanyuan Ying
Ruilin Chen
Zhen Wang
Xin Lv
author_facet Xiaoqing Zhou
Xiaoqing Zhou
Yingnan Xu
Yuanyuan Ying
Ruilin Chen
Zhen Wang
Xin Lv
author_sort Xiaoqing Zhou
collection DOAJ
description BackgroundImmune checkpoint inhibitors (ICIs) significantly improve survival in lung cancer patients. However, checkpoint inhibitor pneumonitis (CIP) remains a critical safety concern. This meta-analysis systematically evaluates demographic, clinical, and laboratory risk factors associated with CIP development to guide risk-stratified management.MethodsWe systematically searched eight databases from inception to February 20, 2025. Study quality was assessed using the NOS. Adjusted risk factors from multivariate analyses were pooled in RevMan 5.4. Sensitivity analyses addressed heterogeneity, and funnel plots evaluated publication bias.Results28 NOS-certified high-quality studies were included. 20 risk factors comprised: advanced age, male sex, smoking status, preexisting interstitial lung abnormalities, pulmonary fibrosis, COPD, thoracic radiotherapy history, squamous cell carcinoma histology (versus adenocarcinoma), early-stage NSCLC (Stage III versus IV), multifocal metastases (≥2 sites), PD-1 inhibitors (versus PD-L1 agents), elevated PD-L1 expression (≥50%), pembrolizumab use (versus nivolumab), AEC, CRP, PLR, WBC, and hypoalbuminemia. Sensitivity analyses confirmed consistency between FEM and REM; funnel plots indicated no publication bias.ConclusionThis study identifies 20 independent CIP risk factors in ICI-treated lung cancer patients. Early screening and intervention for high-risk populations are critical to reducing CIP incidence and improving clinical outcomes. These findings provide actionable insights for optimizing ICI safety in real-world practice.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/myprospero, identifier CRD420250655469.
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spelling doaj-art-aa127926ad4948c3bd55f6ff09bd575f2025-08-20T02:33:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-05-011610.3389/fimmu.2025.16071701607170Risk factors for checkpoint inhibitor pneumonitis in lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysisXiaoqing Zhou0Xiaoqing Zhou1Yingnan Xu2Yuanyuan Ying3Ruilin Chen4Zhen Wang5Xin Lv6The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, ChinaThe First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaThe First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaThe First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, ChinaThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, ChinaThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, ChinaBackgroundImmune checkpoint inhibitors (ICIs) significantly improve survival in lung cancer patients. However, checkpoint inhibitor pneumonitis (CIP) remains a critical safety concern. This meta-analysis systematically evaluates demographic, clinical, and laboratory risk factors associated with CIP development to guide risk-stratified management.MethodsWe systematically searched eight databases from inception to February 20, 2025. Study quality was assessed using the NOS. Adjusted risk factors from multivariate analyses were pooled in RevMan 5.4. Sensitivity analyses addressed heterogeneity, and funnel plots evaluated publication bias.Results28 NOS-certified high-quality studies were included. 20 risk factors comprised: advanced age, male sex, smoking status, preexisting interstitial lung abnormalities, pulmonary fibrosis, COPD, thoracic radiotherapy history, squamous cell carcinoma histology (versus adenocarcinoma), early-stage NSCLC (Stage III versus IV), multifocal metastases (≥2 sites), PD-1 inhibitors (versus PD-L1 agents), elevated PD-L1 expression (≥50%), pembrolizumab use (versus nivolumab), AEC, CRP, PLR, WBC, and hypoalbuminemia. Sensitivity analyses confirmed consistency between FEM and REM; funnel plots indicated no publication bias.ConclusionThis study identifies 20 independent CIP risk factors in ICI-treated lung cancer patients. Early screening and intervention for high-risk populations are critical to reducing CIP incidence and improving clinical outcomes. These findings provide actionable insights for optimizing ICI safety in real-world practice.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/myprospero, identifier CRD420250655469.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1607170/fullmeta-analysischeckpoint inhibitor pneumonitisimmune checkpoint inhibitorsrisk factorimmune-related adverse events
spellingShingle Xiaoqing Zhou
Xiaoqing Zhou
Yingnan Xu
Yuanyuan Ying
Ruilin Chen
Zhen Wang
Xin Lv
Risk factors for checkpoint inhibitor pneumonitis in lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
Frontiers in Immunology
meta-analysis
checkpoint inhibitor pneumonitis
immune checkpoint inhibitors
risk factor
immune-related adverse events
title Risk factors for checkpoint inhibitor pneumonitis in lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
title_full Risk factors for checkpoint inhibitor pneumonitis in lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
title_fullStr Risk factors for checkpoint inhibitor pneumonitis in lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
title_full_unstemmed Risk factors for checkpoint inhibitor pneumonitis in lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
title_short Risk factors for checkpoint inhibitor pneumonitis in lung cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
title_sort risk factors for checkpoint inhibitor pneumonitis in lung cancer patients treated with immune checkpoint inhibitors a systematic review and meta analysis
topic meta-analysis
checkpoint inhibitor pneumonitis
immune checkpoint inhibitors
risk factor
immune-related adverse events
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1607170/full
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