Related Experiment Video
Updated: Jan 18, 2026
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Cardiac Events in Three Phase 3 Randomized Trials Including Acalabrutinib in Chronic Lymphocytic Leukemia
Rupal O'Quinn1, Anthony J Corry2, Naghmana Bajwa2
1Perelman School of Medicine and The Leonard Davis Institute of Health Economics at the University of Pennsylvania, Penn Presbyterian Medical Center, Philadelphia, PA.
Insights
Acalabrutinib, a second-generation Bruton tyrosine kinase (BTK) inhibitor, shows lower cardiac event rates compared to other BTK inhibitors in CLL patients. This improved cardiac safety profile holds true for patients both with and without pre-existing cardiovascular conditions.
Area of Science:
- Oncology
- Pharmacology
- Cardiology
Background:
- First-generation Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective for chronic lymphocytic leukemia (CLL) but carries significant cardiac risks.
- Second-generation BTK inhibitor acalabrutinib offers improved selectivity and a potentially better cardiovascular safety profile than ibrutinib, with fewer atrial fibrillation events.
- There is a need to comprehensively analyze cardiac outcomes associated with acalabrutinib compared to active comparators, particularly in patients with and without baseline cardiovascular disorders.
Purpose of the Study:
- To conduct a comprehensive analysis of cardiac outcomes in patients treated with acalabrutinib versus active comparators, including ibrutinib.
- To evaluate the incidence of cardiac events in patients with and without baseline cardiovascular disorders.
- To compare the safety profile of acalabrutinib concerning cardiac disorders across different treatment arms in Phase 3 trials.
Main Methods:
- Analysis of data from three Phase 3 clinical trials in CLL: ELEVATE-RR, ELEVATE-TN, and ASCEND.
- Calculation of exposure-adjusted incidence rates (EAIR; events/100 person-months) for cardiac disorder events.
- Stratification of analyses by the presence of baseline cardiovascular disorders; all analyses were descriptive without statistical comparisons.
Main Results:
- A total of 1362 patients were included, with 404 (29.7%) having at least one baseline cardiovascular disorder.
- Acalabrutinib demonstrated a lower overall EAIR of any-grade cardiac disorder events compared to active comparators across all trials.
- Acalabrutinib did not increase cardiac events in patients with baseline cardiovascular disorders, and the EAIR of de novo cardiac events was also lower compared to active comparators.
Conclusions:
- The incidence of cardiac disorder events with acalabrutinib was relatively low overall when compared to active comparators.
- Acalabrutinib demonstrated a favorable cardiac safety profile irrespective of the presence of baseline cardiovascular disorders in CLL patients.
- These findings support acalabrutinib as a potentially safer option regarding cardiac toxicity in CLL treatment.
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.
Related Concept Videos
01:11Clinical Trials: Overview
02:56Treatment Resistant Cancers
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...
01:30Acute Coronary Syndrome III: Diagnostic Studies