Fig. 1

Daratumumab mechanisms of action. Upper left: daratumumab binds CD38, and its Fc fragment is bound by C1q, initiating complement cascade and resulting in a MAC which leads to cell lysis and death. Upper right: daratumumab binds CD38, and its Fc fragment is then bound by an FcR-bearing effector cell, such as a natural killer cell, leading to activation of cytotoxic processes. Bottom left: daratumumab binds CD38, and its Fc fragment is then bound by an FcR-bearing macrophage, inducing phagocytosis. Bottom right: FcR-mediated crosslinking of daratumumab induces direct cellular apoptosis. MM cell multiple myeloma cell, CDC complement-dependent cytotoxicity, MAC membrane attack complex, ADCC antibody-dependent cell-mediated cytotoxicity, ADCP antibody-dependent cellular phagocytosis