Safety Drives Decision to Move to Zanubrutinib in CLL

Oncologists are increasingly opting for zanubrutinib (Brukinsa; BeOne Medicines USA, Inc) over ibrutinib (Imbruvica; Pharmacyclics LLC/Janssen Biotech, Inc) to treat patients with chronic lymphocytic leukemia (CLL) due to its improved safety profile and reduced risk of cardiovascular adverse effects, according to Mohit Narang, MD, managing partner at Maryland Oncology Hematology.

Mohit Narang, MD | Image: Johns Hopkins

In a recent interview with The American Journal of Managed Care (AJMC), Narang explained his rationale for switching his patients to the second-generation Bruton tyrosine kinase (BTK) inhibitor. Although ibrutinib has been an effective first-generation BTK inhibitor, Narang saw that patients using it long-term were experiencing adverse effects such as atrial fibrillation (AFib) and stroke—risks that are particularly high for individuals with comorbidities such as hypertension or obesity.1 Narang added that reducing cardiovascular risks is especially important for patients with CLL who have preexisting conditions such as diabetes, obesity, or chronic obstructive pulmonary disease (COPD).

This interview is lightly edited.

AJMC: Can you discuss why you have switched patients with CLL from ibrutinib to zanubrutinib?

Narang: The one big reason is if we have a better product and, as a second-generation drug with low side effects, we have a reason to move from the first generation to the second generation.

AJMC: What specifics in the safety and efficacy data make you prefer zanubrutinib over ibrutinib?

Narang: There [are] a couple of biases. We did the phase 1/2 study with this product, and we found out it was pretty safe from our perspective. Another big reason is [that] we’re in private practice; we have a large practice, and we need to be nimble. So it’s easier to get 1 product associated with CLL, and it gets easier for approval, and my [advanced practice providers] will know that drug the most, compared with understanding all these drugs. That was the one big reason to move [to zanubrutinib]. Second, safety was a big reason because, unfortunately, I had a couple of patients with issues with ibrutinib [when] they’re using it long term, specifically AFib and strokes. So that was my key to move on to the next-generation medication.

AJMC: Is there a length of time a patient should stay on ibrutinib before switching to zanubrutinib? Are you switching all patients or just those with certain clinical features?

Narang: So currently, all our new patients [with CLL]—if they go on BTK, they’re [taking] zanubrutinib (Brukinsa) only. The only patients we have switched are the patients who were inherited from my previous partners. We have been switching for other reasons; patients who have been on ibrutinib for a long time, unfortunately, after all these years, now have weight gain [or] hypertension, both uncontrolled and controlled. Also, there could be COPD.
So these are all the risk factors [that support] converting patients to zanubrutinib. My goal is to prevent a problem, and that was a big reason to switch. In summary, we are switching all our patients, but the specific risk factors, which I tell the patients, [are that] if they’re obese, smokers, [have] hypertension, [or are]…diabetic, unfortunately they already have increased risk. Those are the patients [who] need to be switched as soon as possible.

Reference
Klein HE. In CLL, zanubrutinib shows better safety profile than ibrutinib. AJMC. March 20, 2025. Accessed May 14, 2025. https://www.ajmc.com/view/in-cll-zanubrutinib-shows-better-safety-profile-than-ibrutinib