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Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development

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Department of Internal Medicine, The University of Arizona, Tucson, AZ 85721, USA
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Department of Internal Medicine, Rochester General Hospital, Rochester, NY 14621, USA
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Dow University of Health Sciences, Karachi 74200, Pakistan
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Department of Internal Medicine, University of Pittsburgh Medical Center, McKeesport, PA 16148, USA
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Taussig Cancer Center, Cleveland Clinic, Cleveland, OH 44106, USA
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Foundation University Medical College, Islamabad 44000, Pakistan
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Department of Pathology, Wilson Medical Center, Wilson, NC 27893, USA
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Department of Hematology Oncology, West Virginia University, Morgantown, WV 26506, USA
*
Author to whom correspondence should be addressed.
Antibodies 2019, 8(2), 34; https://doi.org/10.3390/antib8020034
Received: 30 March 2019 / Revised: 12 May 2019 / Accepted: 13 May 2019 / Published: 24 May 2019
(This article belongs to the Special Issue Antibody-Based Therapeutics for Treating Cancer)
Background: Immunotherapy for multiple myeloma (MM) has been the focus in recent years due to its myeloma-specific immune responses. We reviewed the literature on non-Food and Drug Administration (FDA) approved monoclonal antibodies (mAbs) to highlight future perspectives. We searched PubMed, EMBASE, Web of Science, Cochrane Library and ClinicalTrials.gov to include phase I/II clinical trials. Data from 39 studies (1906 patients) were included. Of all the agents, Isatuximab (Isa, anti-CD38) and F50067 (anti-CXCR4) were the only mAbs to produce encouraging results as monotherapy with overall response rates (ORRs) of 66.7% and 32% respectively. Isa showed activity when used in combination with lenalidomide (Len) and dexamethasone (Dex), producing a clinical benefit rate (CBR) of 83%. Additionally, Isa used in combination with pomalidomide (Pom) and Dex resulted in a CBR of 73%. Indatuximab Ravtansine (anti-CD138 antibody-drug conjugate) produced an ORR of 78% and 79% when used in combination with Len-Dex and Pom-Dex, respectively. Conclusions: Combination therapy using mAbs such as indatuximab, pembrolizumab, lorvotuzumab, siltuximab or dacetuzumab with chemotherapy agents produced better outcomes as compared to monotherapies. Further clinical trials investigating mAbs targeting CD38 used in combination therapy are warranted. View Full-Text
Keywords: Multiple myeloma; immunotherapy; antibody; targeted therapy; molecular targets; bispecific antibodies; immune checkpoint inhibitors; Antibody Drug Conjugate Multiple myeloma; immunotherapy; antibody; targeted therapy; molecular targets; bispecific antibodies; immune checkpoint inhibitors; Antibody Drug Conjugate
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Iftikhar, A.; Hassan, H.; Iftikhar, N.; Mushtaq, A.; Sohail, A.; Rosko, N.; Chakraborty, R.; Razzaq, F.; Sandeep, S.; Valent, J.N.; Kanate, A.S.; Anwer, F. Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development. Antibodies 2019, 8, 34.

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