B-Cell Maturation Antigen (BCMA) as a Target for New Drug Development in Relapsed and/or Refractory Multiple Myeloma

Int J Mol Sci. 2020 Jul 22;21(15):5192. doi: 10.3390/ijms21155192.

Abstract

During the past two decades there has been a major shift in the choice of agents to treat multiple myeloma, whether newly diagnosed or in the relapsed/refractory stage. The introduction of new drug classes, such as proteasome inhibitors, immunomodulators, and anti-CD38 and anti-SLAMF7 monoclonal antibodies, coupled with autologous stem cell transplantation, has approximately doubled the disease's five-year survival rate. However, this positive news is tempered by the realization that these measures are not curative and patients eventually relapse and/or become resistant to the drug's effects. Thus, there is a need to discover newer myeloma-driving molecular markers and develop innovative drugs designed to precisely regulate the actions of such putative targets. B cell maturation antigen (BCMA), which is found almost exclusively on the surfaces of malignant plasma cells to the exclusion of other cell types, including their normal counterparts, has emerged as a specific target of interest in this regard. Immunotherapeutic agents have been at the forefront of research designed to block BCMA activity. These agents encompass monoclonal antibodies, such as the drug conjugate belantamab mafodotin; bispecific T-cell engager strategies exemplified by AMG 420; and chimeric antigen receptor (CAR) T-cell therapeutics that include idecabtagene vicleucel (bb2121) and JNJ-68284528.

Keywords: BCMA; JNJ-68284528; antibody-drug conjugates; belantamab mafodotin; bispecific T-cell engager; chimeric antigen receptor T-cells; idecabtagene vicleucel; myeloma.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / immunology
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • B-Cell Maturation Antigen / immunology*
  • B-Cell Maturation Antigen / metabolism
  • B-Lymphocytes / immunology
  • Drug Development / methods*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / pathology
  • Neoplasm Recurrence, Local
  • Receptors, Chimeric Antigen / immunology*
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / immunology*

Substances

  • Antibodies, Monoclonal, Humanized
  • B-Cell Maturation Antigen
  • Receptors, Chimeric Antigen
  • TNFRSF17 protein, human
  • TNFSF13 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • belantamab mafodotin