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Review
. 2019 May 24;8(2):34.
doi: 10.3390/antib8020034.

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

Ahmad Iftikhar  1 , Hamza Hassan  2 , Nimra Iftikhar  3 , Adeela Mushtaq  4 , Atif Sohail  5 , Nathaniel Rosko  6 , Rajshekhar Chakraborty  7 , Faryal Razzaq  8 , Sonia Sandeep  9 , Jason Neil Valent  10 , Abraham Sebastian Kanate  11 , Faiz Anwer  12
Affiliations
Review

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

Ahmad Iftikhar et al. Antibodies (Basel). .

Abstract

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.

Keywords: Antibody Drug Conjugate; Multiple myeloma; antibody; bispecific antibodies; immune checkpoint inhibitors; immunotherapy; molecular targets; targeted therapy.

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Conflict of interest statement

F.A. has advisory board membership and participates in speakers’ program of Seattle Genetics and Incyte Corporation. This membership had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. All other authors declare no potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flow diagram. Records identified through PubMed, Embase, Cochrane, SCOPUS and Clinical.Trials.gov database searches.
Figure 2
Figure 2
Bi-specific T-cell engaging antibody (BiTEs) bind tumor cells and immune cells through the interaction of CD3 with antigens on tumor cells.
See this image and copyright information in PMC

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