CHIPping in: Clonal hematopoiesis clinics in community oncology.

Abstract

499 Background: Clonal hematopoiesis of indeterminate prognosis (CHIP) is recently recognized as a pre-malignant condition and independent cardiovascular risk factor with doubled risk of coronary heart disease, cerebrovascular events, and worsened heart failure outcomes. Despite this recognition, multidisciplinary CHIP clinics are near-uniformly associated with tertiary centers where only a minority of oncology patients receive care. Tennessee Oncology is a large community oncology practice with over 200 providers at 35 sites of care throughout Tennessee and North Georgia. Here, we report the characteristics of two years of patients with common CHIP mutations as we prepare to launch our CHIP clinic. Methods: Patients with solid tumors who underwent either tissue- or blood-based comprehensive genomic profiling from May 2021 to May 2023 were reviewed. Patients with incidental discovery of DNMT3A, ASXL1, TET2, JAK2, IDH1/2, SRSF2, U2AF1, SF3B1, and ZRSR2 mutations are classified as having CHIP. High-risk mutation profile was defined as >1 mutation or a single mutation with variant allele frequency (VAF) of ≥10%. In patients sequenced >1x, only initial sequencing was used. The presence of cardiovascular disease or traditional risk factors was based entries into the patients’ “problem list” or use of medications commonly used to treat these conditions. Results: Over a two-year period, 3599 patients underwent sequencing and CHIP mutations were identified in 1069 (29.7%) patients. The median VAF was 1.58% and 585 patients had at least one mutation with a VAF of ≥2%. Median age at sequencing was 69.6 years. Distribution between males/females was similar. Lung cancer was the most common histology (n=328) followed by breast (n=122) and colon (n=121). DNMT3A mutations (n=829) were most frequently seen followed by TET2 (n=353), ASXL1 (n=335), SRSF2/U2AF1/SF3B1/ZRSR2 (n=147), JAK2 (n=138), and IDH1/2 (n=104). Nearly two-thirds of patients had a high-risk mutational profile with >1 mutation (n=479) or VAF ≥10% (n=185). Assessing traditional risk factors for cardiovascular and cerebrovascular disease, essential hypertension and type 2 diabetes were present in 56.4% (n=603) and 30.1% (n=322) of patients, respectively, and a minority of patients had established coronary disease (n=181) or heart failure (n=74). Twenty-three percent (245/1069) had no cardiovascular risk factors. Conclusions: In a large community practice, 29.7% of patients have common CHIP mutations – most of whom are considered high-risk based on current risk stratification criteria. Many patients also have traditional risk factors or established cardiac disease underscoring the strong association between CHIP and cardiovascular disease. A community-based, multi-disciplinary CHIP clinic would enhance these patients’ care and potentially lead to improved outcomes.