Mechanisms of Resistance to Anti-CD38 Daratumumab in Multiple Myeloma
Ilaria Saltarella, Vanessa Desantis, Assunta Melaccio, Antonio Giovanni Solimando, Aurelia Lamanuzzi, Roberto Ria, Clelia Tiziana Storlazzi, Maria Addolorata Mariggiò, Angelo Vacca, Maria Antonia Frassanito
Abstract
Daratumumab (Dara) is the first-in-class human-specific anti-CD38 mAb approved for the treatment of multiple myeloma (MM). Although recent data have demonstrated very promising results in clinical practice and trials, some patients do not achieve a partial response, and ultimately all patients undergo progression. Dara exerts anti-MM activity via antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and immunomodulatory effects. Deregulation of these pleiotropic mechanisms may cause development of Dara resistance. Knowledge of this resistance may improve the therapeutic management of MM patients.