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// Jai N. Patel 1 , 2 , Jai Singh 3 and Nilanjan Ghosh 2 , 4 1 Department of Cancer Pharmacology and Pharmacogenomics, Atrium Health Levine Cancer Institute, Charlotte, NC 28204, USA 2 Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC 27157, USA 3 Sanger Heart and Vascular Institute, Atrium Health, Charlotte, NC 28204, USA 4 Department of Hematologic Malignancies and Blood Disorders, Atrium Health Levine Cancer Institute, Charlotte, NC 28204, USA Correspondence to: Nilanjan Ghosh, email: nilanjan.ghosh@atriumhealth.org Keywords: BTK inhibitor; cardiotoxicity; biomarkers; risk; genetics Received: May 13, 2024 Accepted: May 21, 2024 Published: June 03, 2024 Copyright: © 2024 Patel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Ibrutinib was the first Bruton's tyrosine kinase (BTK) inhibitor approved for the treatment of patients with chronic lymphocytic leukemia (CLL). While producing durable responses and prolonging survival, roughly 20–25% of patients experience dose limiting side effects, mostly consisting of cardiovascular toxicities like severe hypertension and atrial fibrillation. While clinical predictors of BTK inhibitor-related cardiotoxicity have been proposed and may aid in risk stratification, there is no routine risk model used in clinical practice today to identify patients at highest risk. A recent study investigating genetic predictors of ibrutinib-related cardiotoxicity found that single nucleotide polymorphisms in KCNQ1 and GATA4 were significantly associated with cardiotoxic events. If replicated in larger studies, these biomarkers may improve risk stratification in combination with clinical factors. A clinicogenomic risk model may aid in identifying patients at highest risk of developing BTK inhibitor-related cardiotoxicity in which further risk mitigation strategies may be explored.
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