Acalabrutinib monotherapy is associated with a low incidence of cardiac adverse events (AEs) in patients with chronic lymphocytic leukemia (CLL), according to researchers.

In a retrospective analysis, published in Haematologica, 17% of acalabrutinib-treated patients had cardiac AEs of any grade.

The analysis included data from 762 patients enrolled on 4 clinical trials (ClinicalTrials.gov Identifiers: NCT02029443, NCT02475681, NCT02970318, and NCT02337829).


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The patients initially received oral acalabrutinib at total daily doses of 100 mg to 400 mg, which were subsequently reduced to 100 mg twice daily, until disease progression or toxicity. The patients’ median age was 67 years (range, 32-89 years).

The median follow-up was 25.9 months. The median duration of acalabrutinib exposure was 24.9 months, with 553 patients still receiving acalabrutinib at the data cutoff.

In all, 199 cardiac AEs of any grade were noted in 17% of patients (129/762). The most common of these were atrial fibrillation (4%), palpitations (3%), and tachycardia (2%).

There were 51 grade 3 or higher AEs reported in 37 patients (5%). Twelve patients had a grade 4 AE, and 2 had a grade 5 AE. However, there were no sudden cardiac deaths reported.

The median time to onset of cardiac AEs was 10.1 months, and these AEs led to treatment discontinuation in 7 patients (1%).

Of the 129 patients with cardiac AEs, 91% had at least 1 cardiovascular risk factor before starting acalabrutinib. Of the 38 patients with atrial fibrillation/flutter AEs, 7 (18%) had a history of atrial fibrillation/flutter or arrhythmia.

Hypertension AEs were reported in 67 patients (9%), a majority of whom had relapsed/refractory CLL (58%). The median time to a hypertension AE was 6.5 months.

Of the 67 patients with hypertension AEs, 43 (64%) had pre-existing hypertension. The most common risk factors other than pre-existing hypertension were hyperlipidemia (19%), hypercholesterolemia (19%), diabetes mellitus (10%), coronary artery disease (9%), chronic obstructive pulmonary disease (7%), and coronary artery bypass (6%).

None of the patients discontinued treatment due to hypertension.

“Overall, these data demonstrate a low incidence of new-onset cardiac AEs with acalabrutinib in patients with CLL,” the researchers wrote.

They added that findings from a randomized trial comparing ibrutinib and acalabrutinib in patients with high-risk CLL (ClinicalTrials.gov Identifier: NCT02477696) should reveal any differences in cardiovascular toxicity between the 2 drugs.

Disclosures: This research was supported by Acerta Pharma as well as funding from foundations and government agencies. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Brown JR, Byrd JC, Ghia P, et al. Cardiovascular adverse events in patients with chronic lymphocytic leukemia receiving acalabrutinib monotherapy: Pooled analysis of 762 patients. Haematologica. Published online September 30, 2021. doi:10.3324/haematol.2021.278901