Figure 1. (from left to right): Myeloma-associated macrophages (MAMs) regularly fail to exert MOR202-mediated cytotoxicity against MM cells, due to their impaired vitamin D metabolic pathway and reduced expression of CYP27B1.

This reduced CYP27B1 expression can be overcome by lenalidomide, which significantly increases the expression of CYP27B1, leading to an increased conversion of 25D3 into bioactive 1,25D3. Increased 1,25D3 level promote CD38 target expression on MM cells and combination of lenalidomide and exogenously added 25D3 improves the efficacy of MOR202-mediated cytotoxicity of MAMs.