Anti-Cd20 And B-Cell Receptor-Mediated Growth Inhibition And Apoptosis: A Preclinical Study Of Ibrutinib And Rituximab Combination Therapy In Mantle Cell Lymphoma In Vitro And In Vivo

Intruduction Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with poor outcome and therapeutic challenge. Oral single-agent ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, elicited a response rate of 68% in phase II clinical trial and has been approved by FDA for the treatment of MCL patients who received at least one prior therapy. To increase the response rate, the combination of ibrutinib with rituximab would be an ideal regimen because: (1) Both BTK and CD20 are effective therapeutic targets for MCL; (2) CD20-dependent apoptosis occurs associated with B-cell receptor (BCR) activity. Regardless rituximab-mediated immune response (ADCC and CDC) and ibrutinib-mediated ITK inhibition (Th1 polarization), an important potential effect of ibrutinib and rituximab may enhance the direct anti-MCL cytotoxicity of the combination.