Key Data on Hypertension and Atrial Fibrillation in Patients With CLL
Ricardo Parrondo, MD, discusses that in treating chronic lymphocytic leukemia, BTK inhibitors like ibrutinib can pose cardiovascular risks, including hypertension; he suggests that in choosing a BTK inhibitor one should consider the patient's preexisting cardiovascular conditions.
Asher A. Chanan-Khan, MD, MBBS: One thing, Dr Parrondo, which is a very common adverse effect and a very common known issue in the population that we treat in CLL [chronic lymphocytic leukemia], is hypertension, underlying hypertension, underlying predisposition to hypertension, and so forth. And multiple trials are highlighting BTK’s possible adverse effects on hypertension. Dr [Pooja] Advani very nicely hinted that the development of hypertension prior to initiating could be a risk factor for subsequent cardiac events. [Do you have] any comment that you would like to make in context with hypertension, and is that ever a consideration when you’re seeing patients for the first time or second time to sway you away from one or the other?
Ricardo Parrondo, MD: Yes, definitely. As we have previously discussed, patients with preexisting cardiovascular comorbidities, uncontrolled hypertension, atrial fibrillation [AFib], and coronary artery disease, they’re more likely to develop these cardiovascular adverse effects when treated with BTKi [Bruton tyrosine kinase inhibitors]. Some of the data we have are robust data with all the BTKis regarding the incidence of AFib and hypertension. So we have the longest follow-up with ibrutinib from the RESONATE-2 study [NCT01722487], which was single-agent ibrutinib. We have an 8-year follow-up that shows patients over time continue to have a risk of developing AFib and it increases over time. It’s about 7% during years 7 through 8. And the risk of grade 3 AFib is about 6%. Hypertension over time by 8 years is about a 25% risk of developing hypertension with ibrutinib. And then we have good data, comparing ibrutinib with acalabrutinib from the ELEVATE-TN study [NCT02475681]. So, for example, all-grade AFib occurred in 15.6% of patients with ibrutinib, compared with 9% of patients with acalabrutinib. And all-grade hypertension occurred in 22% of patients with ibrutinib, compared with 8.6% of patients with acalabrutinib. So acalabrutinib leads to lower rates of these cardiovascular toxicities compared with ibrutinib.However, from the ALPINE study [NCT03734016], we have data showing AFib is more prevalent with ibrutinib at 12.3% compared with zanubrutinib, but only 4.5%. But interestingly, there is not much difference in the incidence of all-grade hypertension between the two. So patients treated with ibrutinib had a 19.8% incidence of hypertension, and for those with the zanubrutinib, it was 21.9%. So looking at that, comparing across trials, it appears that in terms of hypertension, acalabrutinib might be better and has a lower incidence of hypertension. We’ve pooled data from all the acalabrutinib studies and B-cell malignancies and the incidence of all-grade AFib is 4% and the incidence of all-grade hypertension is 8%. Similarly, we have pooled data from zanubrutinib in all B-cell malignancies and the all-grade AFib rate is 3% and the all-grade hypertension rate is 12%. So, again, it appears that the incidence of hypertension is higher with zanubrutinib and more similar to ibrutinib, whereas acalabrutinib’s incidence of hypertension appears to be a bit lower with BTKi. It definitely helps inform treatment options for [patients with] CLL. So based on this data that I just presented, for somebody with preexisting cardiovascular comorbidities, you don’t necessarily want to deprive them of BTKis, because they are such effective therapies. But you want to tailor which one you use to the patient based on the toxicity profile. So for somebody with difficult-to-control hypertension, I may favor acalabrutinib over zanubrutinib or ibrutinib. And patients who have preexisting AFib, I may stick with zanubrutinib or acalabrutinib as opposed to ibrutinib, because both of those have lower rates of AFib compared with ibrutinib.
