<p>The goal of this study was to identify genetic polymorphisms associated with ibrutinib-related cardiovascular side effects (CVSEs). This is an observational non-interventional pharmacogenomic study of 50 patients with newly diagnosed or relapsed refractory chronic lymphocytic leukemia (NDCLL or RRCLL) receiving ibrutinib 420 mg for at least six months. The ibrutinib-related CVSEs included atrial fibrillation and hypertension, which occurred in 20% of patients. DNA obtained from buccal swabs was genotyped for 40 single nucleotide polymorphisms (SNPs) in <a href="https://www.ncbi.nlm.nih.gov/gene/2626">GATA4</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/6446">SGK1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/3784">KCNQ1</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/3741">KCNA5</a>, <a href="https://www.ncbi.nlm.nih.gov/gene/4878">NPPA</a>, and <a href="https://www.ncbi.nlm.nih.gov/gene/6331">SCN5A</a> using a customized next generation sequencing panel. It was found that GATA4 rs804280 AA (P =.043), KCNQ1 rs163182 GG (P =.036) and KCNQ1 rs2237895 AA (P =.023) were associated with the ibrutinib-related CVSEs. Patients with a high-risk score had at least two of the three significant risk genotypes identified in univariate analysis for GATA4 rs804280 A>C, KCNQ1 rs162182 G>C and KCNQ1 rs2237895 A>C, and patients with a low-risk score had either one or none of these genotypes. In multivariate analysis, 18 patients with at least two of the three high-risk genotypes had an 11.5-fold higher odds of CVSEs (P =.019; 1.79-119.73 at 95% CI). </p>

Genetic Predictors of Ibrutinib-Related Cardiovascular Side Effects in Patients with Chronic Lymphocytic Leukemia