title: Daratumumab: monoclonal antibody therapy to treat multiple myeloma.
abstract: Daratumumab (Darzalex[TM]) is a human monoclonal antibody (MAb) that targets CD38; a surface protein highly expressed across multiple myeloma (MM) cells. Preclinical studies have shown daratumumab induces MM cell death through several mechanisms, including complement-dependent cytotoxicity (CDC) antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), apoptosis upon secondary crosslinking and immunomodulatory effects via a decrease in immune suppressive cells. Daratumumab has a favorable toxicity profile and encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide) and stem cell transplant have already failed. Given the encouraging efficacy and acceptable safety profile, daratumumab has emerged as a novel treatment option for MM both as a monotherapy and in combination with conventional and novel anti-MM agents. This review will focus on preclinical pharmacology, pharmacokinetics, safety and clinical development of daratumumab in MM.
authors.affiliation: Department of Hematology and Medical Oncology, Atlanta VA Medical Center, Atlanta, Georgia, USA.
authors.forename: C
authors.initials: C
authors.lastname: Xia
authors.affiliation: Department of Hematology and Medical Oncology, Atlanta VA Medical Center, Atlanta, Georgia, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ribeiro
authors.affiliation: Department of Hematology and Medical Oncology, Atlanta VA Medical Center, Atlanta, Georgia, USA.
authors.forename: S
authors.initials: S
authors.lastname: Scott
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, USA. sloni01@emory.edu.
authors.forename: S
authors.initials: S
authors.lastname: Lonial
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003165:Complement System Proteins / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C556306:daratumumab; D013792:Thalidomide; D003165:Complement System Proteins; D051997:ADP-ribosyl Cyclase 1; D000077269:Lenalidomide
keywords: Cancer immunotherapy ; Daratumumab; Multiple myeloma