Rapid and Sustained Reduction of Immunosuppressive T-Cells and Focusing of the T-Cell Repertoire in t(11;14) Relapsed/Refractory Multiple Myeloma Patients Treated with Venetoclax in Combination with Daratumumab and Dexamethasone

Background: Venetoclax (Ven) is a highly selective, potent, oral BCL-2 inhibitor that is currently being evaluated as a targeted therapy for the treatment of t(11;14) relapsed/refractory multiple myeloma (RRMM). The combination of Ven with daratumumab (D) and dexamethasone (d) has shown promising efficacy with a tolerable safety profile in the phase 1/2 study (NCT03314181). VenDd is hypothesized to have increased anti-myeloma activity based upon complementary mechanisms of pro-apoptotic effects on tumor cells as well as potentially enhanced T-cell activation and clonal expansion, which has been shown to be associated with achieving deep sustained response to D-based therapy in MM. Results presented herein describe the immunomodulatory effects observed upon VenDd treatment in t(11;14) RRMM patients, including effects on the T-cell repertoire.