At a median follow-up of 25.9 months, 17% of the patient population who received Calquence monotherapy experienced a cardiac toxicity of any severity, which led to treatment discontinuation in only seven patients.
Treatment with single-agent Calquence (acalabrutinib) led to a low incidence of heart-related toxicities in patients with chronic lymphocytic leukemia (CLL), which resulted in very few treatment discontinuations, according to data from an analysis of four clinical trials presented at the 2020 ASH Annual Meeting and Exposition.
“In this analysis, cardiac events occurred in 17% of patients with CLL who were treated (with Calquence) monotherapy and rarely resulted in discontinuation. (The majority) of patients with cardiac (adverse events) had pre-existing risk factors,” Dr. Jennifer R. Brown, director of the CLL Center at Dana-Farber Cancer Institute, said during a virtual presentation of the data. “Overall, these data suggest a low risk of cardiac (adverse events) with (Calquence) in patients with CLL.”
Although Bruton tyrosine kinase inhibitors have been demonstrated to be effective in the treatment of B-cell malignancies, previous study results have shown an increase in cardiovascular toxicities associated with the use of Imbruvica (ibrutinib). However, since Calquence is a more selective BTK inhibitor than Imbruvica in lab tests, the researchers hypothesized that single-agent Calquence may have a more favorable toxicity profile.
As a result, Brown and colleagues conducted a pooled analysis of data from four clinical trials to assess cardiovascular toxicities associated with Calquence administered as a single agent in patients with CLL. The goal was to evaluate the incidence, seriousness and severity of the heart-related events in these patients and determine if there was an association between the drug and the toxicities.
Researchers also assessed the time to onset of cardiac events and event duration, event management and resolution of toxicities that were more serious or severe, and the incidence of these events within the first six months of treatment.
Data included in this analysis were collected from four studies in which 762 patients with CLL were treated with one or more doses of Calquence.
At a median follow-up of 25.9 months, 17% of the patient population who received Calquence monotherapy experienced a cardiac toxicity of any severity, which led to treatment discontinuation in only seven patients. Notably, the data demonstrated that 91% of patients who experienced a cardiac toxicity had at least one or more pre-existing risk factor before receiving Calquence.
Thirty-seven patients experienced 51 cardiac events that were considered more serious or severe. Of those patients, 49% continued to receive Calquence monotherapy at the time researchers stopped collecting data. Those individuals who stopped receiving treatment did so because of either acute myocardial infarction (two patients), congestive cardiac failure (two patients), cardiac failure (one patient) and cardiac tamponade (one patient). Moreover, four patients stopped therapy as a result of other toxicities, five stopped because their disease progressed, three discontinuations occurred because of patient death, and one was attributed to other reasons.
Seventy-one percent of the 51 cardiac events were managed with the use of concomitant medications and 84% of them were resolved.
Additional data demonstrated that the median time to onset of cardiac events was 10.1 months with a median event duration of 0.2 months. Of 38 patients who experienced atrial fibrillation/flutter while receiving treatment, 18% had a prior history of arrhythmia or atrial fibrillation/flutter. Of 67 patients who experienced hypertension events while receiving Calquence, 69% had prior hypertension and 27% had risk factors.
The most common cardiac event of any severity that occurred in patients treated with Calquence included atrial fibrillation (44 events), palpitations (27 events) and tachycardia (17 events).
A version of this story originally appeared on OncLive® as “Pooled Analysis of 4 Clinical Trials Reflects Low Cardiac Risk With Acalabrutinib in CLL.”
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