Acalabrutinib Is Not Associated With Increased Hypertension Risk in CLL

Treatment with acalabrutinib (Calquence) does not increase the risk for developing new or worsening hypertension in patients with chronic lymphocytic leukemia (CLL), according to Alessandra Ferrajoli, MD, who emphasized the importance of recognizing the baseline rate of hypertension and other comorbidities in patients with this disease. 

“As we gain experience with BTK inhibitors, we gain experience with their activity, and we are learning more about their unique toxicities,” Ferrajoli said in an interview with OncLive® following the 2023 ASH Annual Meeting. “This helps us decide which BTK inhibitor is best for each patient.”

At the meeting, Ferrajoli and colleagues presented findings from a cumulative study investigating the prevalence of hypertension in patients with CLL and other hematologic malignancies who received acalabrutinib. This study demonstrated that the incidence of hypertension in patients with CLL treated with acalabrutinib was similar to that in patients with CLL who had not yet been treated.¹

In the interview, Ferrajoli discussed the research needs for describing the risk of hypertension associated with the various BTK inhibitors, key findings from the cumulative review presented at the 2023 ASH Annual Meeting, and the importance of involving patients in shared decision making when determining their treatment plans.

Ferrajoli is the associate medical director and a professor in the Department of Leukemia, in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.

OncLive: What was the rationale for conducting a cumulative review of hypertension in patients with CLL who received acalabrutinib? What did this study find?

Ferrajoli: We wanted to conduct a cumulative review of hypertension in patients treated with acalabrutinib because there are indications from prior studies that acalabrutinib may not influence blood pressure as much as other TKIs or BTK inhibitors. [Using data from a large database], we compared both the incidence and prevalence of hypertension [in patients with CLL who received acalabrutinib with that in patients before they] started any kind of therapy [for CLL]. We also compared the incidence of hypertension in the whole database [of patients with CLL who received acalabrutinib with that in] patients who were part of randomized trials where they received ibrutinib [Imbruvica].

Our review confirmed what we suspected: that the incidence of hypertension in patients treated with acalabrutinib is superimposable to the incidence of hypertension in this [CLL] population, which is mostly made up of older male adults.

What factors might influence your decision to prescribe acalabrutinib vs other BTK inhibitors for patients with CLL who have hypertension?

[In] a patient with CLL who has particularly difficult-to-control hypertension or hypertension that already needs multiple agents to achieve control, I would prefer acalabrutinib so I would not anticipate any additional needs in the management of that patient’s hypertension. [I would also consider acalabrutinib] if [a patient has] other [risk] factors for hypertension, such [obesity, a smoking history], or any other factor that makes me think hypertension is a potential problem, mostly based on the patient’s medical history.

How do you weigh the potential benefits of acalabrutinib against the risks associated with this drug for patients with CLL and hypertension?

BTK inhibitors revolutionized the treatment of patients with CLL. The potential benefit [of acalabrutinib] is that as we [achieve] control of the disease, the overall health status of the patient will also improve. Obtaining control of the disease [is worth taking] a small risk of cardiovascular toxicities that are a class effect of these drugs. Overall, it’s a small price to pay compared with the toxicities of treatments in the past, such as chemoimmunotherapy, which is what we used to treat patients with CLL 20 years ago. However, with BTK inhibitors, treatment often needs to be prolonged. [Since these agents are] given over time, we have now become attuned and attentive to chronic toxicities [associated with these drugs].

What is the importance of understanding the findings from this study of hypertension in CLL in the context of common baseline characteristics in this patient population?

Regarding the cardiovascular toxicities, as well as other toxicities, such as other cancers, that are relatively common in patients with CLL, we need to [take] a global view of these patients. These patients are older and tend to be White. They have a lot of comorbidities by the time they require treatment for CLL. They may have had other cancers, some cardiovascular events, stents, and maybe even a degree of renal insufficiency.

It’s important to know the baseline in this population. This was reported previously for atrial fibrillation. We can’t expect this population to have a rate of atrial fibrillation of 0. There is a baseline rate of those comorbidities, and adding a BTK inhibitor increases the risk for [developing them].

How do you involve patients in shared decision making when considering the decision to use acalabrutinib or other BTK inhibitors?

This is important. I sit with my patients and have long discussions [with them] regarding what toxicities are [possible] and what monitoring they should do. For example, regarding hypertension, I ask my patients to keep a log of their blood pressure at home, so they can have an idea of what their blood pressure is in real life. I practice in Houston, which is a large city with a lot of traffic. When patients come to my clinic, they tend to justify non-optimal control of their blood pressure [by saying it is] related to the [events of the day, such as] fighting traffic, coming to clinic, and the anxiety of seeing the doctor and finding out what’s going on with their disease. I engage them and tell them I want them to monitor themselves, [because] I need to know what they do on a regular basis. I ask them to check their blood pressure and keep a log maybe once a week or twice a week, it depends. Of course, if there is uncontrolled hypertension, I will ask them to do it daily.

Then, depending on the situation, I engage either their primary care physician or their cardiologist if they have one. If the patients have multiple risk factors, that’s when I will call in our cardio oncologists, who are the cardiologists at [MD Anderson] who have a lot of experience treating patients on targeted therapy. [I will ask the cardio oncologists to] clear patients for specific treatments or for advice on how to best manage [patients’ disease].

Is there ongoing research in CLL that you would like to highlight?

There is a lot of research going on in patients who receive BTK inhibitors. This research sometimes focuses on more in-depth monitoring, such as continuous monitoring of blood pressure, but also continuous monitoring for arrhythmias. We will learn much more once these data can be reported and published.

We will see what happens during the therapy once the therapy is initiated. What changes do we see in the cardiovascular function of patients? We have the luxury to do this because [BTK inhibitors] are extremely effective and well tolerated. Because of how effective and well tolerated they are in general, we now have an interest in investigating what can be considered the fine-tuning of treatment of patients with BTK inhibitors.

What else were you excited to see at the 2023 ASH Annual Meeting?

The [2023 ASH Annual Meeting] was encouraging and positive regarding the outlook of patients with CLL. We saw many trials reporting efficacy and long-term results of therapy with targeted agents. It was exciting, and it gave us a lot of data to reassure our population about the outlook for patients with CLL.

Editor’s Note: Dr Ferrajoli has disclosed receiving research funding from Beigene, AstraZeneca, AbbVie, and GenMab; and receiving honoraria from AstraZeneca, AbbVie, Janssen, and Genentech.

Reference

Ferrajoli A, Follows G, Marmor Y, et al. Cumulative review of hypertension in patients with chronic lymphocytic leukemia (CLL) and other hematologic malignancies treated with acalabrutinib. Blood. 2023;142(suppl 1):1917. doi:10.1182/blood-2023-174727