Real-World Comparison of Zanubrutinib Versus Acalabrutinib

Authored by Ann Liu, PhD

The Bottom Line:

Real-world data suggests that patients with CLL treated with first-line zanubrutinib have better outcomes than those treated with acalabrutinib.

Who Performed the Research and Where Was it Presented:

Dr. Ryan Jacobs from Atrium Health Levine Cancer Institute and colleagues presented the results at the American Society of Clinical Oncology (ASCO) Annual Meeting in 2026.

Background:

Bruton tyrosine kinase inhibitors (BTKi) revolutionized the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) and greatly improved patient outcomes. Covalent BTKi, which bind irreversibly to BTK, are now commonly used as first-line therapies. Clinical trials have shown that next-generation covalent BTKi acalabrutinib and zanubrutinib offer improved safety profiles over first-generation BTKi ibrutinib. However, acalabrutinib and zanubrutinib have not been directly compared head-to-head in clinical trials. This study compared the real-world effectiveness of acalabrutinib versus zanubrutinib as first-line therapies for CLL / SLL.

Methods and Participants:

This study was a retrospective analysis of real-world patient data from an insurance claims database. It included adult patients diagnosed with CLL / SLL who were treatment-naïve and subsequently received treatment with zanubrutinib (2023 – 2025) or acalabrutinib (2019 – 2025) only.

Results:

• The study included 5,819 patients treated with zanubrutinib and 10,969 patients treated with acalabrutinib, all in the U.S.
• Most patients were male (59-62%) and White (72-73%), and half of the patients were older than 72 years of age.
• Median follow-up was 13 months for the zanubrutinib group and 16 months for the acalabrutinib group.
• After adjusting for demographic and health differences, the zanubrutinib group had longer time to next treatment (how long before patients needed another therapy) and longer overall survival (how long patients were alive) compared with acalabrutinib.
• These differences were statistically significant, but the amount of difference was not reported and may have been only months longer for zanubrutinib, not years.

Conclusions:

This analysis of real-world data suggests that patients with CLL treated with first-line zanubrutinib have better outcomes than patients treated with acalabrutinib, including longer time to next treatment and improved overall survival. Previous studies that indirectly compared zanubrutinib with acalabrutinib in relapsed / refractory CLL have also found similar or better progression-free survival with zanubrutinib. It would also be useful to know how zanubrutinib and acalabrutinib compared in side effect profile and frequency of change of therapy due to intolerance versus disease progression. However, it is unlikely that these two therapies will ever be directly compared in clinical trials, which makes real-world analyses like this one useful.

Links and Resources:

You can read the actual ASCO abstract here: Real-world treatment and survival outcomes for zanubrutinib (zanu) and acalabrutinib (acala) monotherapy among treatment-naive patients with chronic lymphocytic leukemia (CLL) in the United States

Take care of yourself first.

Ann Liu, PhD