Tet2-Driven Clonal Hematopoiesis Predicts Enhanced Response To Canakinumab In The Cantos Trial: An Exploratory Analysis

Clonal Hematopoiesis of Indeterminate Potential (CHIP) is associated with increased risk of atherosclerotic cardiovascular disease and preclinical work in mice has demonstrated that CHIP due to somatic mutations in the TET2 gene leads to accelerated atherosclerosis secondary to activation of the IL-1β signaling pathway. In the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS), canakinumab, an anti-IL-1βantibody, reduced the relative risk of major adverse cardiovascular events (MACE) by 15% in patients with a history of myocardial infarction and increased inflammation as indicated by an hsCRP u003e 2 mg/L. To identify CHIP(+) patients enrolled in the CANTOS trial, we performed targeted deep sequencing of genes previously associated with CHIP in a subset (n=3925) of CANTOS trial participants using genomic DNA prepared from baseline peripheral blood samples. We identified 344 patients (8.8%) in this subset with evidence for clonal hematopoiesis. As expected, the incidence of CHIP increased with age...