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Prevention Is the Best Treatment: The Case for Understanding the Transition from Monoclonal Gammopathy of Undetermined Significance to Myeloma
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Int. J. Mol. Sci. 2018, 19(12), 3924; https://doi.org/10.3390/ijms19123924

Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update

Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA
Received: 24 October 2018 / Revised: 22 November 2018 / Accepted: 5 December 2018 / Published: 7 December 2018
(This article belongs to the Special Issue Novel Therapeutic Strategies in Multiple Myeloma)
Full-Text   |   PDF [333 KB, uploaded 7 December 2018]   |   Review Reports

Abstract

The past two decades have seen a revolution in multiple myeloma (MM) therapy with the introduction of several small molecules, mostly orally effective, whose mechanisms are based on proteasome inhibition, histone deacetylase (HDAC) blockade, and immunomodulation. Immunotherapeutic approaches to MM treatment using monoclonal antibodies (mAbs), while long in development, began to reap success with the identification of CD38 and SLAMF7 as suitable targets for development, culminating in the 2015 Food and Drug Administration (FDA) approval of daratumumab and elotuzumab, respectively. This review highlights additional mAbs now in the developmental pipeline. Isatuximab, another anti-CD38 mAb, currently is under study in four phase III trials and may offer certain advantages over daratumumab. Several antibody-drug conjugates (ADCs) in the early stages of development are described, including JNJ-63723283, which has attained FDA breakthrough status for MM. Other mAbs described in this review include denosumab, recently approved for myeloma-associated bone loss, and checkpoint inhibitors, although the future status of the latter combined with immunomodulators has been clouded by unacceptably high death rates that caused the FDA to issue clinical holds on several of these trials. Also highlighted are the therapies based on the B Cell Maturation Antigen (BCMA), another very promising target for anti-myeloma development. View Full-Text
Keywords: myeloma; daratumumab; elotuzumab; isatuximab; CD38; JNJ-63723283; denosumab; checkpoint inhibitors; BCMA; bispecific T-cell engager; antibody-drug conjugates myeloma; daratumumab; elotuzumab; isatuximab; CD38; JNJ-63723283; denosumab; checkpoint inhibitors; BCMA; bispecific T-cell engager; antibody-drug conjugates
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Abramson, H.N. Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update. Int. J. Mol. Sci. 2018, 19, 3924.

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