Switching Patients With CLL From Ibrutinib for Zanubrutinib: Mohit Narang, MD

Oncologists are increasingly opting for zanubrutinib over ibrutinib to treat patients with chronic lymphocytic leukemia (CLL) due to its improved safety profile and reduced risk of cardiovascular side effects, according to Mohit Narang, MD, managing partner at Maryland Oncology Hematology.

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. While ibrutinib has been an effective first-generation BTK inhibitor, Narang saw that patients using it long-term were experiencing adverse effects like atrial fibrillation (AFib) and stroke—risks that are particularly high for individuals with comorbidities such as hypertension or obesity. Narang added that reducing cardiovascular risks is especially important for patients with CLL who have preexisting conditions like diabetes, obesity, or chronic obstructive pulmonary disease (COPD).

Another advantage of switching to zanubrutinib is its practicality within a large oncology practice. Having a single, safer option can streamline treatment protocols, simplify drug approvals, and facilitate training for advanced practice providers (APPs), Narang explained.

“It’s easier to get 1 product associated with CLL, and it gets easier for approval,” he said. “And my APPs will know the drug the most compared to understanding all these drugs.”

Currently, Narang has made a complete transition for new patients with CLL patients requiring BTK inhibitors, with zanubrutinib being the standard choice. For existing patients previously on ibrutinib, those with comorbid conditions such as obesity, hypertension, diabetes, or a smoking history—factors that increase the risk of AFib—are being prioritized for switching.

A recent study comparing the 2 treatments found a superior safety profile for zanubrutinib, with fewer serious adverse events and lower rates of treatment discontinuation due to toxicity.1 The 200-person study also showed that patients taking zanubrutinib experienced significantly fewer cardiovascular complications like AFib and hypertension compared with those on ibrutinib.

Hematologic toxicities, such as neutropenia, were also less common in the zanubrutinib group. Although the difference in severe adverse events was not statistically significant, the trend toward fewer complications was considered clinically meaningful, particularly for patients who are older or frailer and need to maintain stable blood counts.

In addition to its favorable safety profile, zanubrutinib may also offer cost savings compared with ibrutinib for patients with relapsed or refractory CLL. An economic analysis based on the ALPINE trial showed that treating 100 patients with zanubrutinib instead of ibrutinib could save approximately $4.7 million over 24 months.2 This cost advantage stems from zanubrutinib’s lower drug costs and improved progression-free survival, making it a potentially more cost-effective choice for managed care settings.

References

1. 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
2. Kaltwasser J. Zanubrutinib may lead to cost savings vs ibrutinib in R/R CLL. AJMC. April 15, 2025. Accessed May 14, 2025. https://www.ajmc.com/view/zanubrutinib-may-lead-to-cost-savings-vs-ibrutinib-in-r-r-cll