Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor that is very effective for treating chronic lymphocytic leukemia (CLL). However, it must be taken continuously for an indefinite duration, and its use has been linked to increased risk of developing cardiovascular side effects (a.k.a. adverse events) such as atrial fibrillation, ventricular arrhythmias, and hypertension. Researchers don’t know exactly why ibrutinib causes these cardiovascular adverse events, and they have been investigating whether these effects occur with next-generation BTK inhibitors, such as acalabrutinib.
At the annual meeting of the American Society of Hematology (ASH) 2020, our own Steven Bloom interviewed Dr. Jennifer Brown, Director of the CLL Center at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. They discussed how often cardiovascular events occur in patients with CLL during acalabrutinib treatment as compared with ibrutinib treatment.
This is a pooled analysis of 4 clinical trials of acalabrutinib in over 700 patients with CLL looking at the frequency of cardiovascular adverse events.
Takeaways:
- 17% of patients experienced any type of cardiovascular adverse event over the 2-year follow-up period. These events ranged from mild, ( a fast heart rate), to life-threatening, ( congestive heart failure), and they were not necessarily related to treatment with acalabrutinib.
- 5% of patients experienced a severe or life-threatening cardiovascular event.
- 4% of patients experienced atrial fibrillation over the 2-year period. This is in line with previous data showing an atrial fibrillation rate of about 6% in patients with untreated CLL. For CLL patients treated with ibrutinib, we might expect a rate of 10-15% over this type of follow-up period.
- Other common adverse events included palpitations, (the feeling that your heart is beating too hard or too fast), and tachycardia (fast heart rate), which are symptoms that can be caused by a variety of conditions and don’t necessarily indicate any underlying cardiovascular problems.
- With ibrutinib there tends to be a peak in serious adverse events in the first 6 months, which wasn’t seen with acalabrutinib. In this analysis, serious adverse events, (grade 3 or higher), were spread evenly across the 2-year period
- Scientists are still waiting on results from a randomized clinical trial directly comparing ibrutinib and acalabrutinib, but the data available thus far seems to indicate that acalabrutinib is safer from a cardiovascular standpoint.
Conclusions:
Next-generation BTK inhibitors such as acalabrutinib may be a safer option for patients with cardiovascular disease risk factors, ( hypertension, hyperlipidemia, arrhythmias, etc). The results of this analysis indicate that there is low risk of cardiovascular adverse events with acalabrutinib treatment.
Please enjoy this interview with Dr. Brown from the virtual ASH meeting which was held December 2020.
You can read the actual ASH abstract here: Pooled Analysis of Cardiovascular Events from Clinical Trials Evaluating Acalabrutinib Monotherapy in Patients with Chronic Lymphocytic Leukemia (CLL)
Take care of yourself first.
Ann Liu, PhD
