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
Affiliations
Ilaria Saltarella
Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
Vanessa Desantis
Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
Assunta Melaccio
Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
Antonio Giovanni Solimando
Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
Aurelia Lamanuzzi
Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
Roberto Ria
Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
Clelia Tiziana Storlazzi
Department of Biology, University of Bari “Aldo Moro”, 70125 Bari, Italy
Maria Addolorata Mariggiò
Department of Biomedical Sciences and Human Oncology, Unit of General Pathology, University of Bari “Aldo Moro”, 70124 Bari, Italy
Angelo Vacca
Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine and Clinical Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
Maria Antonia Frassanito
Department of Biomedical Sciences and Human Oncology, Unit of General Pathology, University of Bari “Aldo Moro”, 70124 Bari, Italy
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.
