zanubrutinib + rituximab

Zanubrutinib plus rituximab is a combination therapy used primarily for the treatment of B-cell malignancies such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Zanubrutinib is a next-generation, highly selective Bruton tyrosine kinase inhibitor (BTKi) that irreversibly binds to BTK, blocking B-cell receptor signaling which is critical for malignant B-cell survival and proliferation. Rituximab is an anti-CD20 monoclonal antibody that targets CD20 on B-cells leading to their destruction via immune-mediated mechanisms including antibody-dependent cellular cytotoxicity and phagocytosis. The combination aims to improve efficacy over monotherapy by targeting malignant B-cells through complementary mechanisms. This combination has been studied in time-limited regimens in treatment-naïve CLL patients with promising durable remissions and tolerability. It has also been investigated as frontline therapy in MCL with favorable response rates. Zanubrutinib offers improved selectivity compared to first-generation BTK inhibitors, resulting in fewer off-target effects and sustained BTK inhibition at therapeutic doses.