Cardiovascular adverse events in patients with chronic lymphocytic leukemia receiving acalabrutinib monotherapy: pooled analysis of 762 patients.

Cardiovascular (CV) toxicities of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib may limit use of this effective therapy in patients with chronic lymphocytic leukemia (CLL). Acalabrutinib is a second-generation BTK inhibitor with greater BTK selectivity. This analysis characterizes pooled CV adverse events (AEs) data in patients with CLL who received acalabrutinib monotherapy in clinical trials (NCT02029443; NCT02475681; NCT02970318; NCT02337829). Acalabrutinib was given orally at total daily doses of 100-400 mg, later switched to 100 mg twice daily, and continued until disease progression or toxicity. Data from 762 patients (median age: 67 years [range, 32-89]; median follow-up: 25.9 months [range, 0-58.5]) were analyzed. Cardiac AEs of any grade were reported in 129 patients (17%; grade ≥3, n=37 [5%]) and led to treatment discontinuation in 7 patients (1%). The most common any-grade cardiac AEs were atrial fibrillation/flutter (5%), palpitations (3%), and tachycardia (2%). Overall, 91% of patients with cardiac AEs had CV risk factors before acalabrutinib treatment. Among 38 patients with atrial fibrillation/flutter events, 7 (18%) had prior history of arrhythmia or atrial fibrillation/flutter. Hypertension AEs were reported in 67 patients (9%), 43 (64%) of whom had a preexisting history of hypertension; no patients discontinued treatment due to hypertension. No sudden cardiac deaths were reported. Overall, these data demonstrate a low incidence of new-onset cardiac AEs with acalabrutinib in patients with CLL. Findings from the head-to-head, randomized trial of ibrutinib and acalabrutinib in patients with high-risk CLL (NCT02477696) will prospectively assess differences in CV toxicity between the two agents