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dc.contributor.authorMcEllistrim, Cian
dc.contributor.authorKrawczyk, Janusz
dc.contributor.authorO'Dwyer, Michael
dc.date.accessioned2018-09-20T16:16:58Z
dc.date.available2018-09-20T16:16:58Z
dc.date.issued2017-04-01
dc.identifier.citationMcEllistrim, Cian; Krawczyk, Janusz; O'Dwyer, Michael (2017). New developments in the treatment of multiple myeloma – <br />clinical utility of daratumumab. Biologics: Targets and Therapy 11 , 31-43
dc.identifier.issn1177-5491
dc.identifier.urihttp://hdl.handle.net/10379/12769
dc.description.abstractMultiple 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.
dc.publisherDove Medical Press Ltd.
dc.relation.ispartofBiologics: Targets and Therapy
dc.subjectmultiple myeloma
dc.subjectmonoclonal antibodies
dc.subjectdaratumumab
dc.subjectimmunotherapy
dc.subjectcd38
dc.subjectminimal residual disease
dc.subjectcd38 monoclonal-antibody
dc.subjectlenalidomide plus dexamethasone
dc.subjectaccess treatment protocol
dc.subjectunited-states patients
dc.subjectt-cell expansion
dc.subjecttargeting cd38
dc.subjectup-regulation
dc.subjectprior lines
dc.subjectopen-label
dc.subjectcombination
dc.titleNew developments in the treatment of multiple myeloma – <br />clinical utility of daratumumab
dc.typeArticle
dc.identifier.doi10.2147/btt.s97633
dc.local.publishedsourcehttps://www.dovepress.com/getfile.php?fileID=35952
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