Here we aim at developing a combination therapy for myeloma by combining a new CD38 antibody (GenMab), lenalidomide and bortezomib. In vitro assays are designed to determine the best combination of the drugs to induce NK cell mediated, antibody dependent cytotoxicity (ADCC), complement mediated cytotoxicity (CDC) against myeloma cells. So far we observed a synergistic effect between lenalidomide and anti-CD38 antibodies to improve ADCC. The optimal in vitro combinations are being tested in the animal model for human myeloma for their capacity to eliminate myeloma.