A real‐world data analysis of the impact of clonal hematopoiesis of indeterminate potential on therapeutic efficacy and adverse events of immune checkpoint inhibitors

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) has been implicated in systemic inflammation. Although immune checkpoint inhibitors (ICIs) have transformed cancer care, their response rates remain modest, and some patients experience severe immune-related adverse events (irAEs). This study investigated whether CHIP affects ICI treatment efficacy and safety in patients with advanced solid tumors. METHODS: Data from 2040 individuals with advanced solid tumors who underwent liquid biopsy-based gene panel testing and received ICI therapy (with or without chemotherapy) were retrospectively analyzed. CHIP was defined as the presence of mutations in DNMT3A, TET2, or ASXL1 at a variant allele frequency ≥0.02. Overall response rate (ORR), disease control rate (DCR), real-world time to discontinuation (TTD), and the incidence of grade ≥3 irAEs were compared between CHIP-positive and CHIP-negative groups. RESULTS: CHIP was detected in 25.7% of cases. CHIP-positive group exhibited significantly prolonged TTD (median, 10.1 vs. 7.9 months; hazard ratio, 0.81; p = .005). Gene-specific analyses showed that TET2 was independently associated with longer TTD (median, 10.3 vs. 8.2 months; hazard ratio, 0.77; p = .035), whereas DNMT3A displayed a similar but nonsignificant trend. In contrast, ASXL1-positive patients had a lower ORR yet still showed a trend toward longer TTD. No significant association was observed between CHIP and the incidence of grade ≥3 irAEs. CONCLUSION: In this real-world cohort, CHIP, particularly TET2 mutations, was associated with prolonged ICI treatment duration. These findings suggest that CHIP may serve as a potential biomarker for predicting the clinical benefit of ICIs in advanced solid tumors.