Therapeutic effect and mechanism of ibrutinib combined with dexamethasone on multiple myeloma.

Abstract

Ibrutinib is an irreversible inhibitor of Bruton s tyrosine kinase and has proven to be an effective agent for B-cell-mediated hematological malignancies, including multiple myeloma (MM). Several clinical trials of ibrutinib treatment combined with dexamethasone (DXMS) for relapsed MM have demonstrated high response rates, however, the mechanism still remains unclear. In this study, we explored the therapeutic effect and mechanism of ibrutinib combined with DXMS on MM in vitro and vivo. The apoptosis of MM cell lines and mononuclear cells from MM patients bone marrow induced by ibrutinib combined with DXMS was detected by flow cytometry and the expression of apoptosis-related proteins were detected by Western blot. A mice MM model was established to verify the therapeutic effect of ibrutinib combined with DXMS on MM. We found that ibrutinib combined with DXMS increased the apoptosis of MM cell lines through the PI3K/PARP pathway, significantly reduced CD38 expression in MM cells from patients in vitro, and reduced tumor size and increased the survival time in mice model. This study provides a theoretical basis for the treatment of relapsed refractory MM with ibrutinib combined with DXMS, and a potential therapeutic target for MM clinical treatment.