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

• Published in: Haematologica (Roma) Vol. 107; no. 6; pp. 1335 - 1346
• Main Authors: Brown, Jennifer R, Byrd, John C, Ghia, Paolo, Sharman, Jeff P, Hillmen, Peter, Stephens, Deborah M, Sun, Clare, Jurczak, Wojciech, Pagel, John M, Ferrajoli, Alessandra, Patel, Priti, Tao, Lin, Kuptsova-Clarkson, Nataliya, Moslehi, Javid, Furman, Richard R
• Format: Journal Article
• Language: English
• Published: Italy Fondazione Ferrata Storti 01.06.2022; Ferrata Storti Foundation
• Subjects: Aged; Atrial Fibrillation; Benzamides; Chronic Lymphocytic Leukemia; Humans; Hypertension; Leukemia, Lymphocytic, Chronic, B-Cell - complications; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Protein Kinase Inhibitors - adverse effects; Pyrazines
• ISSN: 0390-6078; 1592-8721; 1592-8721
• DOI: 10.3324/haematol.2021.278901

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 (AE) data in patients with CLL who received acalabrutinib monotherapy in clinical trials (clinicaltrials gov. Identifier: NCT02029443, NCT02475681, NCT02970318 and 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 AE of any grade were reported in 129 patients (17%; grade ≥3, n=37 [5%]) and led to treatment discontinuation in seven patients (1%). The most common any-grade cardiac AE were atrial fibrillation/flutter (5%), palpitations (3%), and tachycardia (2%). Overall, 91% of patients with cardiac AE had CV risk factors before acalabrutinib treatment. Among 38 patients with atrial fibrillation/flutter events, seven (18%) had prior history of arrhythmia or atrial fibrillation/flutter. Hypertension AE 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 AE with acalabrutinib in patients with CLL. Findings from the head-to-head, randomized trial of ibrutinib and acalabrutinib in patients with highrisk CLL (clinicaltrials gov. Identifier: NCT02477696) prospectively assess differences in CV toxicity between the two agents.