Daratumumab in multiple myeloma

• Published in: Cancer Vol. 125; no. 14; pp. 2364 - 2382
• Main Authors: Nooka, Ajay K., Kaufman, Jonathan L., Hofmeister, Craig C., Joseph, Nisha S., Heffner, Thomas L., Gupta, Vikas A., Sullivan, Harold C., Neish, Andrew S., Dhodapkar, Madhav V., Lonial, Sagar
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 15.07.2019
• Subjects: ADP-ribosyl Cyclase 1 - immunology; ADP-ribosyl Cyclase 1 - metabolism; Amyloidosis - drug therapy; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antigens; Antineoplastic Agents, Immunological - administration & dosage; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - pharmacology; Antineoplastic Agents, Immunological - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; CD38 antigen; CD38 monoclonal antibody; Clinical trials; daratumumab; Drug development; Drug Evaluation, Preclinical; Drug Resistance, Neoplasm; Humans; Immunotherapy; Immunotherapy - methods; Induction therapy; infusion reactions; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Monoclonal antibodies; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; myeloma; myeloma management; Oncology; Patients; Survival Rate; Target recognition; Targeted cancer therapy; Treatment Outcome; infusion reactions; myeloma; daratumumab; myeloma management; CD38 monoclonal antibody
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.32065

The development of effective monoclonal antibodies for the treatment of myeloma has been a long journey of clinical and drug development. Identification of the right target antigen was a critical part of the process. CD38 as a target has been considered for some time, but clinically, daratumumab, a CD38 monoclonal antibody, was the first to be tested, and it has delivered the best clinical responses as a single agent to date. Its proven safety and efficacy in combination with other antimyeloma agents have led to several US Food and Drug Administration approvals for treating myeloma. Furthermore, the results of early trials in the induction therapy setting have demonstrated a beneficial role when it is added to the existing induction regimens. This review summarizes the importance of CD38 as a target and examines the clinical development of the CD38 monoclonal antibody daratumumab and its clinical significance in combination regimens in both patients with relapsed/refractory myeloma and patients with newly diagnosed myeloma. Daratumumab is the first CD38 monoclonal antibody to deliver unprecedented clinical responses as a single agent in heavily pretreated patients with myeloma, and this had led to several US Food and Drug Administration approvals for treating myeloma. Daratumumab in the first‐line setting has demonstrated a beneficial role as an addition to the existing induction regimens for patients with newly diagnosed myeloma.