Healthcare Resource Utilization and Costs in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia Treated With Covalent Bruton's Tyrosine Kinase Inhibitors: Real-World Impact of Cardiovascular Adverse Events.

INTRODUCTION: Although covalent Bruton's tyrosine kinase inhibitors (cBTKis) have transformed treatment of chronic lymphocytic leukemia and small lymphocytic leukemia (CLL/SLL), cBTKi-related cardiotoxicity is a known side effect. This real-world study evaluated incident cardiovascular adverse events (CVAE), healthcare resource utilization (HCRU), and costs among patients with CLL/SLL receiving cBTKis. METHODS: Adult patients with CLL/SLL who initiated ibrutinib or acalabrutinib treatment (index date) between 2020 and 2023 were identified using US claims data and followed up to 36 months post-index. Incident CVAEs (not present pre-index) were assessed during cBTKi treatment and patients were stratified by CVAE status. HCRU and costs were evaluated per 1000 patient-months (PPPM). RESULTS: Overall, 2069 patients were identified (mean age of 73.7 ± 9.1 years, 40.4% female) with a mean treatment-specific observation period of 11.4 ± 9.5 months. At least one incident CVAE was observed in 442 (21.4%) patients. The incidence rate was 21.6 PPPM for hypertension, 8.9 PPPM for atrial fibrillation, 8.6 PPPM for ventricular arrhythmias, and 8.3 PPPM for atrial flutter. Patients with incident CVAEs had significantly more total medical service days PPPM (4334 vs. 3138, p < 0.001), primarily driven by increased inpatient (690 vs. 230), outpatient (2798 vs. 2425), other visit (662 vs. 375), and ER days (184 vs. 109) than those without CVAEs. Total healthcare costs (PPPM) were substantially higher for patients with incident CVAEs ($20,250,560 vs. $17,413,460, p < 0.001) mainly due to higher inpatient ($3,417,948 vs. $915,839, p < 0.001), outpatient ($2,415,060 vs. $1,769,628, p < 0.01), and ER costs ($186,820 vs. $87,585, p < 0.001). CONCLUSIONS: The observed class-effect of high CVAEs with cBTKis underscores the unmet need for safer, more selective agents for CLL/SLL treatment. The HCRU and economic burden remain high for CLL/SLL, especially among patients experiencing CVAEs during cBTKi treatment. These findings emphasize the importance of optimizing clinical management to reduce CVAE risk and downstream impacts on HCRU and costs.