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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Frontiers Media S.A.
2025-05-01
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| 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. |
| format | Article |
| id | doaj-art-aa127926ad4948c3bd55f6ff09bd575f |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| 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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