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A Complex DiseaseBCMA as a TargetHealth Disparities in MMResources
B-cell maturation antigen (BCMA) as a therapeutic target in multiple myeloma (MM)1B-cell maturation antigen (BCMA) as a therapeutic target in multiple myeloma (MM)1

The immune system has the natural ability to recognize and eliminate tumor cells—it exerts selective pressure on tumor clones. However, in MM, if the immune response fails to eliminate all tumor cells, variants develop that are able to resist, avoid, or suppress the antitumor immune response.2

MM cells, together with their bone marrow microenvironment, express coinhibitory molecules and immunosuppressive cytokines, leading to immune dysfunction.1,3

 Immune exhaustion in MM

Learn more about the role of immunosuppression in MM

Watch videoLoadingBCMA is a universally present and overexpressed antigen in MM4-6Selectively expressed on plasma cells4,5,7
  • BCMA is a transmembrane glycoprotein of the TNFR superfamily
  • It is expressed on late-stage B-cells and on the surface of plasmablasts and differentiated plasma cells
  • There is minimal expression on hematopoietic stem cells or nonhematopoietic tissue
Associated with disease progression4,8
  • BCMA overexpression and activation can upregulate various pathways and enhance expression of genes critical for survival, growth, metastasis, and immunosuppression
Associated with drug resistance1,7,8
  • BCMA overexpression leads to enhanced expression of IL-10, PD-L1, and other immunoregulatory genes that are thought to suppress the immune response in the bone marrow microenvironment
  • In patients with MM, BCMA is found in increased levels on plasmacytoid dendritic cells, which promote the survival and development of drug resistance in MM cells
 BCMA as a target

See how BCMA can be an immunotherapeutic target in MM

Watch videoLoadingExpert perspectives in MM The role of BCMA in MM

Watch Dr. Landgren talk about the importance of BCMA in MM

Watch videoLoadingIL-10=interleukin 10; PD-L1=programmed death-ligand 1; TNFR=tumor necrosis factor receptor.References:Cho S-F, Anderson KC, Tai Y-T. Targeting B cell maturation antigen (BCMA) in multiple myeloma: potential uses of BCMA-based immunotherapy. Front Immunol. 2018;9:1821. doi:10.3389/fimmu.2018.01821Swann JB, Smyth MJ. Immune surveillance of tumors. J Clin Invest. 2007;117:1137-1146. doi:10.1172/JCI31405Holthof LC, Mutis T. Challenges for immunotherapy in multiple myeloma: bone marrow microenvironment-mediated immune suppression and immune resistance. Cancers (Basel). 2020;12:988. doi:10.3390/cancers12040988Shah N, Chari A, Scott E, Mezzi K, Usmani SZ. B-cell maturation antigen (BCMA) in multiple myeloma: rationale for targeting and current therapeutic approaches. Leukemia. 2020;34:985-1005. doi:10.1038/s41375-020-0734-zCaraccio C, Krishna S, Phillips DJ, Schürch CM. Bispecific antibodies for multiple myeloma: a review of targets, drugs, clinical trials, and future directions. Front Immunol. 2020;11:501. doi:10.3389/fimmu.2020.00501Nadeem O, Tai Y-T, Anderson KC. Immunotherapeutic and targeted approaches in multiple myeloma. Immunotargets Ther. 2020;9:201-215. doi:10.2147/ITT.S240886Tai Y-T, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy. 2015;7:1187-1199. doi:10.2217/imt.15.77Tai Y-T, Acharya C, An G, et al. APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment. Blood. 2016;127:3225-3236. doi:10.1182/blood-2016-01-691162

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