Conference Abstracts Evaluating the Clinical Signifcance of Clonal Hematopoiesis of Indeterminate Potential (CHIP) in patients with Non-Small Cell Lung Cancer (NSCLC) Mason N. Alford 1 , Candace J. Grisham 1 , Christopher Thompson 2 , Wade T. Iams 1 1 Vanderbilt University Medical Center, 2 Tempus Labs, Inc. Keywords: Non-Small Cell Lung Cancer, Lung cancer, oncology, precision oncology https://doi.org/10.53876/001c.38199 International Journal of Cancer Care and Delivery Vol. 2, Issue Supplement 2, 2022 BACKGROUND 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 specifcally patients with non-small cell lung cancer (NSCLC) is in need of fur- ther independent validation. METHODS We partnered with Tempus Labs to analyze cfDNA sequenc- ing 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 circu- lating in a patient’s peripheral blood, including single nu- cleotide 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. RESULTS 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), predom- inance of adenocarcinoma histology (88.8% adenocarci- noma 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), specifcally a thrombus localized to the superior mesenteric vein (SMV). Within the non-CHIP co- hort, 18 of 50 (36%) patients experienced at least one ma- lignant 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 differ- ence was not found to be statistically signifcant (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 signifcant (p=0.4229). CONCLUSION In our single institution, retrospective study, NSCLC pa- tients 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 evalua- tion of differential clinical outcomes among patients with NSCLC with and without CHIP continues to warrant further study in larger groups of patients. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CCBY-SA-4.0). View this license’s legal deed at https://creativecommons.org/licenses/by-sa/4.0 and legal code at https://cre- ativecommons.org/licenses/by-sa/4.0/legalcode for more information. Alford MN, Grisham CJ, Thompson C, Iams WT. Evaluating the Clinical Signifcance of Clonal Hematopoiesis of Indeterminate Potential (CHIP) in patients with Non-Small Cell Lung Cancer (NSCLC). IJCCD. 2022;2(Supplement 2). doi:10.53876/001c.38199