WCLC 2025 - Posters & ePosters-P2.06.71 Clonal Hematopoiesis and Its Association With Lung Cancer Incidence and Immunotherapy Response: A Meta-Analysis

P2.06.71 Clonal Hematopoiesis and Its Association With Lung Cancer Incidence and Immunotherapy Response: A Meta-Analysis

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This meta-analysis evaluated the relationship between clonal hematopoiesis of indeterminate potential (CHIP)—acquired somatic mutations in hematopoietic stem cells without blood cancer—and lung cancer incidence and immunotherapy outcomes. CHIP is implicated in increasing solid tumor risks through inflammation and altered immunity, potentially influencing immune checkpoint inhibitor (ICI) efficacy.<br /><br />The study systematically reviewed eight eligible studies from Embase and Medline databases up to February 2025. For lung cancer incidence, analyses included patients without prior lung cancer, followed for new diagnoses. For ICI response, lung cancer patients treated with ICIs were assessed for overall survival (OS). Hazard ratios (HRs) and odds ratios (ORs) were meta-analyzed, including subgroup analyses based on smoking history and specific CHIP gene mutations (ASXL1, DNMT3A, TET2).<br /><br />Findings demonstrated that CHIP presence was significantly associated with increased lung cancer incidence (HR 1.40; 95% CI 1.29–1.53), a risk consistent regardless of smoking history (HR ~1.4 for smokers and non-smokers). Among lung cancer patients receiving ICIs, CHIP status did not significantly impact OS (HR 1.04; 95% CI 0.58–1.87), indicating no adverse effect on immunotherapy survival outcomes. Subgroup analysis by gene mutations revealed differential risk: ASXL1 mutation had the highest lung cancer risk (HR 1.81), followed by DNMT3A (HR 1.66) and TET2 (HR 1.36).<br /><br />The authors concluded that CHIP elevates lung cancer risk irrespective of smoking, with genetic variability influencing the magnitude of risk. However, CHIP does not appear to worsen survival in lung cancer patients treated with ICIs. These results highlight the need for further research into CHIP's role in cancer risk stratification and the biological mechanisms underlying these associations, which may inform targeted screening and personalized management for at-risk populations.

Asset Subtitle

Dhruv Bansal

Meta Tag

Speaker Dhruv Bansal

Topic Pathology and Biomarkers

Keywords

clonal hematopoiesis of indeterminate potential

CHIP

lung cancer incidence

immune checkpoint inhibitors

immunotherapy outcomes

ASXL1 mutation

DNMT3A mutation

TET2 mutation

smoking history

cancer risk stratification