Preprint Review Version 1 This version is not peer-reviewed

Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update

Version 1 : Received: 24 October 2018 / Approved: 24 October 2018 / Online: 24 October 2018 (12:11:23 CEST)

A peer-reviewed article of this Preprint also exists.

Abramson, H.N. Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update. Int. J. Mol. Sci. 2018, 19, 3924. Abramson, H.N. Monoclonal Antibodies for the Treatment of Multiple Myeloma: An Update. Int. J. Mol. Sci. 2018, 19, 3924.

Journal reference: Int. J. Mol. Sci. 2018, 19, 3924
DOI: 10.3390/ijms19123924

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 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 therapies based on the B Cell Maturation Antigen (BCMA), another very promising target for anti-myeloma development.

Subject Areas

myeloma; daratumumab; elotuzumab; isatuximab; CD38; JNJ- 63723283; denosumab; checkpoint inhibitors; BCMA; bispecific T-cell engager; antibody-drug conjugates

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