BTKi-induced cardiovascular toxicity in CLL: Risk mitigation and management strategies

Abstract

Targeted therapies, consisting of Bruton tyrosine kinase inhibitors (BTKis) or BCL-2 inhibitors, are the mainstay of contemporary treatments for chronic lymphocytic leukemia (CLL). The most common adverse effects (AEs) of BTKis are fatigue, bruising, infection, hematological and cardiovascular AEs. While AEs during treatment are usually mild (grades 1 and 2), grade 3 and 4 AEs have been detected in some patients, necessitating additional medical care and temporary or permanent drug discontinuation. In this review, we analyzed the cardiovascular effects associated with BTKi therapy for CLL and the essential practical aspects of multidisciplinary management of patients who develop cardiovascular toxicity during treatment. We particularly focus on the data and strategies for controlling cardiovascular risks associated with ibrutinib and newer BTKis (acalabrutinib, zanubrutinib and pirtobrutinib), including the development of atrial fibrillation, hypertension, ventricular arrhythmias, sudden death, heart failure, bleeding, and ischemic complications (stroke and myocardial infarction). This review highlights hematological insights underlying cardiotoxicity, an area that has received limited attention in comparison to the predominantly cardiological perspective. This review synthesizes emerging evidence on hematological biomarkers, cardiotoxic mechanisms, and therapeutic interventions, linking hematology and cardiology to enhance understanding and guide comprehensive prevention and management strategies.

Keywords: Atrial fibrillation; Bleeding; Bruton tyrosine kinase inhibitors; Cardiotoxicity; Chronic lymphocytic leukemia; Heart failure; Hypertension.