1. Bruton's tyrosine kinase inhibitor-related cardiotoxicity: The quest for predictive biomarkers and improved risk stratification.
- Author
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Patel JN, Singh J, and Ghosh N
- Subjects
- Humans, Adenine analogs & derivatives, Adenine adverse effects, Risk Assessment, Pyrimidines adverse effects, Pyrazoles adverse effects, Biomarkers, Polymorphism, Single Nucleotide, KCNQ1 Potassium Channel genetics, Tyrosine Kinase Inhibitors, Agammaglobulinaemia Tyrosine Kinase antagonists & inhibitors, Agammaglobulinaemia Tyrosine Kinase genetics, Protein Kinase Inhibitors adverse effects, Cardiotoxicity etiology, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Piperidines adverse effects, Piperidines therapeutic use
- 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.
- Published
- 2024
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