Costs and consequences of cardiovascular toxicity due to Bruton's tyrosine kinase inhibitors in chronic lymphocytic leukemia.

[INTRODUCTION AND OBJECTIVES] BTK inhibitors (BTKis) have revolutionized the treatment landscape of chronic lymphocytic leukemia (CLL). However, a higher risk of cardiovascular toxicity is reported among CLL patients treated with BTKis. This study aims to estimate the costs and consequences of cardiovascular toxicity associated with the different BTKis used for CLL treatment in Portugal.

[METHODS] The incidence rates and health-related outcomes consequences among CLL patients, including bleeding events, de novo atrial fibrillation (AF) and hypertension were retrieved from the literature for the different BTKis. Direct medical costs (payers' perspective) associated with diagnosis, monitoring and treatment of cardiovascular toxicity were calculated for one year. Inpatient costs were derived from the Portuguese Hospital Morbidity Database. Outpatient costs were estimated from an expert panel.

[RESULTS] Incidence rates per 100 CLL BTKis-treated patients ranged from 38.0 (acalabrutinib) to 70.3 (zanubrutinib) for bleeding, from 5.4 (zanubrutinib) to 14.9 (ibrutinib) for AF, and from 6.6 (acalabrutinib) to 36.7 (zanubrutinib) for hypertension. Incidence rates of health outcomes related to AF (stroke and heart failure) were higher among ibrutinib-treated patients, whereas health outcomes related to hypertension (angina, myocardial infarction, heart failure and peripheral arterial disease) were higher among zanubrutinib-treated patients. Total costs per 100 CLL BTKis-treated patients over the first year were EUR 38803.10, EUR 82683.61, and EUR 86084.56 for acalabrutinib, zanubrutinib, and ibrutinib, respectively. In subsequent years, costs decreased by 47%, 43%, and 39%, respectively.

[CONCLUSION] The clinical and economic burden of cardiovascular toxicity associated with BTKis treatment among CLL patients is high, with ibrutinib showing the highest impact in comparison to the more selective BTKis.