Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Dec 19;12(1):15.
doi: 10.3390/cancers12010015.

Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma

Francesca Bonello  1 , Roberto Mina  1 , Mario Boccadoro  1 , Francesca Gay  1
Affiliations
Review

Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma

Francesca Bonello et al. Cancers (Basel). .

Abstract

Immunotherapy is the latest innovation for the treatment of multiple myeloma (MM). Monoclonal antibodies (mAbs) entered the clinical practice and are under evaluation in clinical trials. MAbs can target highly selective and specific antigens on the cell surface of MM cells causing cell death (CD38 and CS1), convey specific cytotoxic drugs (antibody-drug conjugates), remove the breaks of the immune system (programmed death 1 (PD-1) and PD-ligand 1/2 (L1/L2) axis), or boost it against myeloma cells (bi-specific mAbs and T cell engagers). Two mAbs have been approved for the treatment of MM: the anti-CD38 daratumumab for newly-diagnosed and relapsed/refractory patients and the anti-CS1 elotuzumab in the relapse setting. These compounds are under investigation in clinical trials to explore their synergy with other anti-MM regimens, both in the front-line and relapse settings. Other antibodies targeting various antigens are under evaluation. B cell maturation antigens (BCMAs), selectively expressed on plasma cells, emerged as a promising target and several compounds targeting it have been developed. Encouraging results have been reported with antibody drug conjugates (e.g., GSK2857916) and bispecific T cell engagers (BiTEs®), including AMG420, which re-directs T cell-mediated cytotoxicity against MM cells. Here, we present an overview on mAbs currently approved for the treatment of MM and promising compounds under investigation.

Keywords: B cell maturation antigens (BCMAs); antibody products; bispecific T cell engagers (BiTEs®); immunotherapy; monoclonal antibodies (mAbs); multiple myeloma (MM).

PubMed Disclaimer

Conflict of interest statement

F.B. declares no competing financial interests. R.M. has received honoraria from Amgen, Celgene, Takeda, and Janssen, and served on the advisory boards for Janssen. M.B. has received honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers Squibb, and AbbVie, and has received research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers Squibb, and Mundipharma. F.G. has received honoraria from Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda, and served on the advisory boards for Amgen, Bristol-Myers Squibb, Celgene, Janssen, Roche, Takeda, and AbbVie.

Figures

Figure 1
Figure 1
Main mechanisms of action of anti-CD38 monoclonal antibodies. Abbreviations: MDSC, myeloid-derived suppressor cell; ADCC, antibody-dependent cell-mediated cytotoxicity; CDC, complement-dependent cytotoxicity; NAD, nicotinamide adenine dinucleotide; ADPR, adenosine ribose; MAC, membrane attack complex.
See this image and copyright information in PMC

References

    1. Turesson I., Velez R., Kristinsson S.Y., Landgren O. Patterns of Improved Survival in Patients with Multiple Myeloma in the Twenty-First Century: A Population-Based Study. J. Clin. Oncol. 2010;28:830–834. doi: 10.1200/JCO.2009.25.4177. - DOI - PMC - PubMed
    1. Kristinsson S.Y., Anderson W.F., Landgren O. Improved long-term survival in multiple myeloma up to the age of 80 years. Leukemia. 2014;28:1346–1348. doi: 10.1038/leu.2014.23. - DOI - PubMed
    1. Howlader N., Noone A., Krapcho M., Miller D., Brest A., Yu M., Ruhl J., Tatalovich Z., Mariotto A., Lewis D., et al. SEER Cancer Statistics Review (CSR), 1975-2016. National Cancer Institute; Bethesda, MD, USA: 2019. [(accessed on 19 December 2019)]. (Based on November 2018 SEER Data Submission, Posted to the SEER Web Site, April 2019). Available online: https://seer.cancer.gov/csr/1975_2016/
    1. Kumar S., Paiva B., Anderson K.C., Durie B., Landgren O., Moreau P., Munshi N., Lonial S., Bladé J., Mateos M.-V., et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet. Oncol. 2016;17:e328–e346. doi: 10.1016/S1470-2045(16)30206-6. - DOI - PubMed
    1. Attal M., Lauwers-Cances V., Hulin C., Leleu X., Caillot D., Escoffre M., Arnulf B., Macro M., Belhadj K., Garderet L., et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N. Engl. J. Med. 2017;376:1311–1320. doi: 10.1056/NEJMoa1611750. - DOI - PMC - PubMed