Impact of Treatment Duration on Development of BTKi-Related Atrial Fibrillation in Patients With CLL
Ricardo Parrondo, MD, explains that different BTK inhibitors have varying rates of cardiovascular side effects in patients with chronic lymphocytic leukemia, suggesting the choice between them should consider a patient's preexisting cardiovascular conditions, with acalabrutinib favored for hypertension concerns and zanubrutinib for atrial fibrillation issues.
Asher A. Chanan-Khan, MD, MBBS: Dr Parrondo, would you like to comment on the cardiac and hypertensive adverse effects profile, for example, from the larger trials such as those with ibrutinib—the ELEVATE-TN study [NCT02475681] and the ALPINE study [NCT03734016]—and the pooled data that have come out.
Ricardo Parrondo, MD Yes, we have robust data comparing ibrutinib with acalabrutinib from the ELEVATE-TN study and data comparing ibrutinib with zanubrutinib from the ALPINE study in relapsing CLL [chronic lymphocytic leukemia]. The ELEVATE-TN study shows the incidence of all-grade atrial fibrillation [AFib] was 15.6% with ibrutinib vs 9% with acalabrutinib, so lower rates of all-grade AFib. But when you look at the rate of grade 3 or greater AFib, it was more similar between the 2 drugs where patients with ibrutinib had 3.4%, grade 3 or greater AFib, whereas acalabrutinib had 4.5% grade 3 or greater AFib. And then in terms of hypertension, all-grade hypertension occurred in 22% of patients with ibrutinib, compared to 8.6% of patients with acalabrutinib. And then grade 3 or greater hypertension was also higher, with ibrutinib at 8.7% vs 4.1% with acalabrutinib. So in terms of AFib, he all grades, there was more AFib with ibrutinib compared with acalabrutinib, but grade 3 or greater AFib events were pretty similar between the 2 drugs. However, in terms of hypertension, ibrutinib had a higher rate of all-grade hypertension and grade 3 or greater hypertension. Now, when you look at ALPINE comparing zanubrutinib with ibrutinib, it’s a little bit reverse. So the all-grade AFib was 12% with ibrutinib compared with 4.5% with zanubrutinib and then the grade 3 or greater AFib was 3.7% with ibrutinib compared with 1.9% with zanubrutinib. So all-grade and grade 3 or greater AFib is less with zanubrutinib compared with ibrutinib. Whereas when you look at ELEVATE-TN, the all-grade AFib with ibrutinib was higher compared with acalabrutinib, but the grade 3 or greater was pretty similar. Whereas with zanubrutinib, it was lower than ibrutinib. But then, in contrast to the ELEVATE-TN of acalabrutinib and ibrutinib, we saw lower rates of all-grade hypertension and grade 3 or greater hypertension with acalabrutinib compared with ibrutinib. In ALPINE, we see pretty similar rates of all-grade hypertension and grade 3 or greater hypertension between ibrutinib and zanubrutinib So when it comes time to select a BTK inhibitor in patients with preexisting cardiovascular comorbidities, or somebody with poorly controlled hypertension, I would tend to use acalabrutinib because the rate of hypertension, both all grade and grade 3, is definitely lower compared with ibrutinib. And then for somebody with AFib or preexisting AFib, I would tend to use zanubrutinib because the rates of all grade AFib and grade 3 or greater AFib are lower.
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