ReviewOncology and therapy2026
A Comprehensive Review of the Role of Zanubrutinib for Patients with Chronic Lymphocytic Leukemia.
Review in Oncology and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Abstract
The approval of ibrutinib over a decade ago introduced Bruton tyrosine kinase (BTK) inhibition as a foundational, chemotherapy-free treatment approach for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). A continuous single-agent BTK inhibitor (BTKi) or a time-limited B cell lymphoma 2 inhibitor (BCL2i)-based regimen plus an anti-CD20 monoclonal antibody or BTKi is now standard of care for CLL/SLL. Although ibrutinib offers durable remission for many patients, its use is limited by side effects associated with inhibition of kinases other than BTK (off-target effects). The second-generation BTKi zanubrutinib was developed to provide sustained BTK inhibition with greater selectivity for BTK in order to improve clinical efficacy and tolerability with minimized off-target effects. The head-to-head ALPINE study of patients with relapsed/refractory (R/R) CLL/SLL demonstrated superior efficacy with zanubrutinib versus ibrutinib, with superior overall response rates and prolonged progression-free survival (PFS), while acalabrutinib demonstrated non-inferior PFS outcomes versus ibrutinib in patients with high-risk R/R CLL/SLL. Data also showed improved safety outcomes with zanubrutinib versus ibrutinib with significantly lower rates of atrial fibrillation/flutter, and infection, and a trend toward lower rates of other adverse events associated with ibrutinib, with the exception of neutropenia. This is reflected in treatment guidelines for CLL, where zanubrutinib and the other approved second-generation BTKi, acalabrutinib, are recommended over ibrutinib owing to their superior safety profiles (particularly reduced cardiotoxicity). In this review, we consider the pharmacologic properties of zanubrutinib that differentiate it from ibrutinib and acalabrutinib, and provide a comprehensive overview of the efficacy and safety data that led to zanubrutinib monotherapy becoming a preferred therapy for a significant subgroup of patients with CLL/SLL. We also highlight trials in CLL/SLL and Richter's transformation with zanubrutinib in targeted therapy combinations that offer the potential for time-limited treatment courses.
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