Clonal hematopoiesis of Indeterminate Potential (CHIP) is the age-related acquisition of somatic mutations leading to the clonal expansion of hematopoietic stem cells. Blood-based next generation sequencing (NGS) cell free DNA (cfDNA) assays in patients with NSCLC can detect canonical CHIP-driver mutations (e.g DNMT3A, TET2, ASXL1).1 While CHIP has been associated with an increased risk of hematological malignancy,2 coronary heart disease,3 and worsened all-cause mortality,4 the relationship between CHIP and clinical outcomes among specifically patients with non-small cell lung cancer (NSCLC) is in need of further independent validation.
We partnered with Tempus Labs to analyze cfDNA sequencing data from patients with NSCLC for the presence of CHIP. This sequencing data is derived from the Tempus xF ® cfDNA assay, which detects genomic alterations circulating in a patient’s peripheral blood, including single nucleotide variants (SNVs)/insertions and deletions (indels) in 105 genes, copy number gains (CNGs) in 6 genes, as well as microsatellite instability status. Clinical outcomes for NSCLC patients were analyzed through retrospective chart review under institutional review board approved protocol #211701.
Overall, 60 NSCLC patients were included (n=9 patients with CHIP ; n=51 patients without CHIP). Demographically, the CHIP and non-CHIP cohorts demonstrated comparable mean age at diagnosis (68.1 years vs. 65.5 years), predominance of adenocarcinoma histology (88.8% adenocarcinoma vs. 88.2% adenocarcinoma) and advanced clinical stage (88.8% Stage IV vs. 60.8% Stage IV). Within the CHIP cohort, 1 of the 9 patients (11%) experienced a deep vein thrombosis (DVT), specifically a thrombus localized to the superior mesenteric vein (SMV). Within the non-CHIP cohort, 18 of 50 (36%) patients experienced at least one malignant thromboembolic event, with a proportion of DVT (n=10) vs. PE (n=11) vs. Other (n=1). Among patients with stage IV NSCLC, patients with CHIP demonstrated reduced progression-free survival (PFS mean = 294 days) compared to non-CHIP patients (PFS mean = 568 days); this difference was not found to be statistically significant (p=0.2581). Among patients with stage IV NSCLC, patients with CHIP also demonstrated reduced overall survival (OS mean = 529 days) when compared to patients without CHIP (OS mean = 860 days); this difference was not found to be statistically significant (p=0.4229).
In our single institution, retrospective study, NSCLC patients with CHIP were found to have reduced incidence of malignant thromboembolic events as compared to non-CHIP controls. We also observed a trend towards inferior PFS and OS outcomes for patients with stage IV NSCLC with CHIP compared to non-CHIP controls. Overall, the evaluation of differential clinical outcomes among patients with NSCLC with and without CHIP continues to warrant further study in larger groups of patients.