BCMA-targeting approaches for treatment of multiple myeloma

Panminerva Med. 2021 Mar;63(1):28-36. doi: 10.23736/S0031-0808.20.04121-X. Epub 2020 Sep 21.

Abstract

Recent advances in treatment modalities have led to improved survival in patients with multiple myeloma (MM). However, despite these, MM remains an incurable disease. Many MM patients relapse through and become refractory to current treatment strategies or are intolerant due to toxicities arising from therapy. As such, novel strategies addressing new targets are crucial in improving care for MM patients. BCMA has emerged as a rationale therapeutic target for treatment of MM as it is preferentially expressed in mature B-lymphocytes and plasma cells with the overexpression and activation of BCMA via its ligands associated with the disease progression in multiple myeloma. Given the high expression of BCMA in malignant Plasma cells compared to those from normal healthy volunteers, targeting BCMA should reduce risks of on-target off-tumor toxicities. The main BCMA-targeting approaches currently used for treatment of MM include: 1) chimeric antigen receptor (CAR) T-cell therapy; 2) bi- and multi- specific antibodies; and 3) monoclonal antibodies and their drug conjugates. This review will outline these therapeutic agents and present their emerging clinical data.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B-Cell Maturation Antigen / antagonists & inhibitors*
  • B-Cell Maturation Antigen / metabolism
  • Consolidation Chemotherapy
  • Humans
  • Immunotherapy, Adoptive* / adverse effects
  • Molecular Targeted Therapy
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / immunology
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / therapy*
  • Plasma Cells / drug effects*
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • Receptors, Chimeric Antigen / genetics
  • Receptors, Chimeric Antigen / metabolism
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / transplantation*
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • B-Cell Maturation Antigen
  • Receptors, Chimeric Antigen
  • TNFRSF17 protein, human