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New developments in the treatment of multiple myeloma –
clinical utility of daratumumab

Authors McEllistrim C, Krawczyk J, O'Dwyer ME

Received 25 January 2017

Accepted for publication 15 March 2017

Published 11 April 2017 Volume 2017:11 Pages 31—43

DOI https://doi.org/10.2147/BTT.S97633

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Lucy Goodman

Peer reviewer comments 2

Editor who approved publication: Dr Doris Benbrook

Cian McEllistrim,1 Janusz Krawczyk,1 Michael E O’Dwyer1,2

1Department of Hematology, University Hospital Galway, 2Apoptosis Research Centre, Biomedical Sciences, National University of Ireland Galway, Galway, Ireland

Abstract: Multiple myeloma is a clonal disorder of plasma cells that is currently considered incurable. CD38 is a 46 kDa type II transmembrane glycoprotein that is highly expressed on myeloma cells. Daratumumab is a first in-class human IgG1 monoclonal antibody that targets CD38, and has antimyeloma effects through several mechanisms. Single-agent trials show surprising activity in heavily pretreated myeloma patients. Trials in the relapsed setting, where daratumumab is added to lenalidomide and dexamethasone or bortezomib and dexamethasone, have demonstrated significantly improved progression-free survival with acceptable toxicity. In this review, we discuss the mechanism of action, pharmacology and pharmacokinetics of daratumumab and review the available clinical data in detail. We examine how daratumumab interferes with transfusion testing due to the expression of CD38 on the red blood cells, leading to potential difficulties releasing blood products. Daratumumab also affects disease assessments in multiple myeloma, including serum protein electrophoresis, immunofixation and flow cytometry. Strategies to mitigate these effects are discussed. The optimal use of daratumumab has yet to be decided, and several trials are ongoing in the relapsed and upfront setting. We discuss the potential upfront role of this exciting therapy, which has significant potential for increased minimal residual disease negativity and improved progression-free survival even in high-risk groups.

Keywords: multiple myeloma, monoclonal antibodies, daratumumab, immunotherapy, CD38, minimal residual disease

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