Dr Khan on the Role of Zanubrutinib in the Current CLL Treatment Paradigm

"[Zanubrutinib fits into the paradigm] in a multitude of ways. It can be used as a frontline treatment, but it can also be used as relapsed/refractory treatment, provided the patient has not already progressed on a BTK inhibitor [in the] frontline [setting].The other good aspect of zanubrutinib is that you can use it either once daily or twice a day. This allows for flexibility in dosing, which is its main benefit. "

Cyrus M. Khan, MD, an assistant professor of medicine at the Drexel University School of Medicine and the assistant director of the Stem Cell Transplant Program at the Allegheny Health Network Cancer Institute, discusses the role of zanubrutinib (Brukinsa) in the current chronic lymphocytic leukemia (CLL) treatment paradigm.

Khan began by noting that zanubrutinib can be integrated into both frontline and relapsed/refractory settings, provided patients have not previously progressed on a BTK inhibitor in the frontline. In the phase 3 ALPINE trial (NCT03734016), zanubrutinib was associated with improved progression-free survival and overall response rates compared with ibrutinib (Imbruvica) in patients with relapsed/refractory CLL. Moreover, zanubrutinib demonstrated a more favorable safety profile, including lower rates of atrial fibrillation, atrial flutter, and bleeding—adverse effects commonly associated with first-generation BTK inhibitors.

Zanubrutinib’s dosing flexibility offers another practical advantage, with the option for either once-daily or twice-daily administration, allowing clinicians to individualize therapy based on patient preference or tolerability, Khan continued. Beyond CLL, zanubrutinib has gained approval for several other B-cell malignancies, including Waldenström macroglobulinemia, marginal zone lymphoma, and follicular lymphoma in the relapsed/refractory setting, he noted. The agent’s broader utility in these indications has increased clinicians’ comfort and familiarity with its use.

Overall, zanubrutinib’s favorable efficacy, improved tolerability, and broader approval across B-cell malignancies support its role as a preferred BTK inhibitor for appropriate patient populations, Khan concluded. Given the reduced cardiotoxicity and manageable adverse effect profile compared with ibrutinib, zanubrutinib represents a meaningful option in both treatment-naive and relapsed/refractory patients with CLL.