Abstract 17607: Clonal Hematopoiesis of Indeterminate Potential (CHIP) is an Independent Risk Factor for Cardiomyopathy in Patients With Solid Malignancy

Abstract

Background: Somatic mutations linked to clonal hematopoiesis of indeterminate potential (CHIP) are associated with increased risk of cardiomyopathy (CM) and all-cause mortality in the general population. However, this relationship is less clear in patients with solid malignancy, and it is unclear if knowing CHIP status can identify patients at risk for adverse cardiac outcomes. Objectives: To determine the association between CHIP and the development of CM in patients with solid malignancy, as well as overall survival (OS). Methods: CHIP mutation status was determined by next-generation sequencing of DNA from peripheral blood samples of 173 participants with solid malignancy. A somatic variant pipeline using MUTECT2 selected for somatic CHIP variants with a variant of allele frequency between 2-40%. CHIP association with the outcomes of OS and CM was assessed using Kaplan-Meier survival and Cox regression analyses. Results: Participants’ median age was 63 years, and 76% were female. CHIP mutations were detected in 39% of participants, most commonly in DNMT3A, TET2, and IDH2 genes. Majority were breast cancer patients 54% (n= 94). More patients with CHIP had diastolic dysfunction (21% vs 9%, p=0.037) compared to those without CHIP. After a median follow-up of 36 months, those with CHIP had an earlier time to death and earlier time to CM. Cox regression analysis showed that metastatic disease (HR 2.92, P=0.003) and male gender (HR 2.35, P=0.03) were independent risk factors for death, and CHIP (HR 2.120, P=0.02) was an independent risk factor for CM (Figure). Conclusions: Our study showed that solid malignancy patients with CHIP had worse outcomes with shorter time to death and shorter time to CM, with CHIP being an independent risk factor for CM. CHIP assessment can help us identify patients who may be at greater risk for adverse cardiovascular events during and after cancer therapy and who may warrant closer monitoring.