Cardiac Events in Three Phase 3 Randomized Trials Including Acalabrutinib in 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.