Acalabrutinib had lower exposure-adjusted incidence rates of de novo cardiac events versus active comparators across three trials (e.g., 0.34 vs 0.67 events/100 person-months vs ibrutinib).
Does acalabrutinib reduce cardiac disorder events compared to active comparators in patients with chronic lymphocytic leukemia?
Acalabrutinib demonstrates a favorable cardiovascular safety profile with lower rates of cardiac events compared to other targeted therapies, including ibrutinib, in patients with chronic lymphocytic leukemia.
BACKGROUND: The first-generation Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in patients with CLL but is associated with considerable cardiac toxicity. The more selective second-generation BTK inhibitor acalabrutinib has demonstrated a more favorable cardiovascular safety profile with fewer atrial fibrillation events versus ibrutinib. We performed a comprehensive analysis of cardiac outcomes with acalabrutinib versus active comparators, including ibrutinib, in patients with and without baseline cardiovascular disorders. MATERIALS AND METHODS: Data from three phase 3 trials in CLL (ELEVATE-RR, ELEVATE-TN, ASCEND) were used. Exposure-adjusted incidence rates (EAIR; events/100 person-months) were reported for system organ class "cardiac disorders" in patients overall and by number of baseline cardiovascular disorders. All analyses were descriptive. No statistical comparisons were performed. RESULTS: In total, 1362 patients were included; 404 (29.7%) had ≥1 baseline cardiovascular disorder. The overall EAIR of any-grade cardiac disorder events was lower for acalabrutinib versus active comparator in each trial, and acalabrutinib did not increase cardiac events in patients with ≥1 baseline cardiovascular disorder. The EAIR of de novo cardiac disorder events (ie, among patients without baseline cardiovascular disorders) was also lower for acalabrutinib versus active comparator across trials (ELEVATE-RR: 0.34 vs. 0.67 acalabrutinib vs. ibrutinib, ELEVATE-TN: 0.28 and 0.25 vs. 0.59 acalabrutinib plus obinutuzumab and acalabrutinib vs. chlorambucil + obinutuzumab, ASCEND: 0.28 vs. 0.44 and 0.54 acalabrutinib vs. idelalisib plus rituximab and bendamustine plus rituximab). CONCLUSIONS: The EAIRs of cardiac disorder events was relatively low overall with acalabrutinib versus comparators, regardless of the presence of baseline cardiovascular disorders.
O’Quinn et al. (2025) studied Chronic Lymphocytic Leukemia (n=1,362). Acalabrutinib vs. Active comparators (ibrutinib, chlorambucil + obinutuzumab, idelalisib + rituximab, bendamustine + rituximab) was evaluated on Exposure-adjusted incidence rates (EAIR; events/100 person-months) for cardiac disorders. Acalabrutinib had lower exposure-adjusted incidence rates of de novo cardiac events versus active comparators across three trials (e.g., 0.34 vs 0.67 events/100 person-months vs ibrutinib).