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Mechanisms of Resistance to Anti-CD38 Daratumumab in Multiple Myeloma.

Ilaria SaltarellaVanessa DesantisAssunta MelaccioAntonio Giovanni SolimandoAurelia LamanuzziRoberto RiaClelia Tiziana StorlazziMaria Addolorata MariggiòAngelo VaccaMaria Antonia Frassanito
Published in: Cells (2020)
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.
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