OBJECTIVES: cBTKis revolutionized CLL/SLL treatment following ibrutinib’s approval in 2014. Second-generation cBTKis—acalabrutinib and zanubrutinib—displayed enhanced CVD safety profiles. This research evaluated the real-world treatment patterns and pre-treatment CVD burden in CLL/SLL patients.

METHODS: Adult patients diagnosed with CLL/SLL who received cBTKi treatment were identified using Optum Clinformatics® DataMart claims data (2014-2023). Patients with other cBTKi-related malignancies or prior CLL/SLL-related anticancer treatment were excluded. Pre-2020 (2014-2019) and post-2020 (2020-2023) periods were assessed to capture the impact of acalabrutinib’s launch in late 2019. Lines of treatment (LOTs) from first-line (1L) to fifth-line (5L) were evaluated.

RESULTS: Overall, 4,353 patients (39.7% female) were eligible with a median age of 73, mean National Cancer Institute Comorbidity Index of 0.5, and average observation period of 2.8 years. cBTKi use was prevalent across all LOTs and decreased from 81.4% in the 1L to 45.7% in the 5L. 1L cBTKi use increased from 70.5% pre-2020 to 94.8% post-2020, while chemoimmunotherapy use declined from 19.8% to 2.6%. Among cBTKis, 1L ibrutinib use decreased from 69.6% pre-2020 to 52.9% post-2020, while acalabrutinib use increased from 0.9% to 36.9%. Switching or restarting (re-initiation after 90-day gap) among cBTKis (cBTKi→cBTKi) was the most common pathway and increased from 21.3% pre-2020 to 41.3% post-2020. The 2L restart rate for ibrutinib (16.7%) was consistent for pre- and post-2020 periods, whereas it increased from 0.4% to 9.5% for acalabrutinib. Pre-treatment CVD prevalence was high for acalabrutinib and ibrutinib, including ventricular arrhythmias (14.8% and 12.2%), congestive heart failure (14.8% and 11.0%), atrial fibrillation (14.3% and 9.5%), and atrial flutter (11.2% and 7.5%).

CONCLUSIONS: Our findings showed high uptake of cBTKis as 1L treatment, with frequent restart of cBTKis and a considerable pre-treatment CVD burden across CLL/SLL treatments. Further real-world investigation is crucial to understand CVD risks and clinical/health economics outcomes associated with cBTKis.