Current antibody-based therapies for the treatment of multiple myeloma

Clin Adv Hematol Oncol. 2020 Nov;18(11):736-748.

Abstract

Despite continued and considerable progress following the introduction of proteasome inhibitors and immunomodulatory agents, multiple myeloma (MM) remains an incurable disease, and new therapeutic strategies are urgently needed. Monoclonal antibodies represent a well-established targeted approach to the treatment of MM, with selective killing properties and limited off-target toxicity. Since their approval, the anti-CD38 agent daratumumab, the anti-SLAMF7 agent elotuzumab, and most recently the anti-CD38 agent isatuximab have led to pivotal improvements in the treatment of double-refractory MM; currently, they are on their way to becoming integral parts in the up-front care of patients who have newly diagnosed MM, with daratumumab already approved in this setting. Several other antibody-based strategies are undergoing clinical assessment in MM. Although the investigation of checkpoint inhibitors in MM has been halted, bispecific T-cell engagers and especially antibody-drug conjugates demonstrate encouraging efficacy and manageable toxicity in triple class-refractory MM. The accelerated approval of belantamab mafodotin represents an important milestone in antibody development; its ability to target B-cell maturation antigen (BCMA) in advanced disease is now established. Here, we present an overview of the currently available monoclonal antibody treatments in MM and discuss the clinical value, significant potential, and possible limitations of these immunotherapeutic approaches to driving deeper responses and achieving longer overall survival among patients with a challenging disease.

Publication types

  • Review

MeSH terms

  • ADP-ribosyl Cyclase 1 / antagonists & inhibitors
  • ADP-ribosyl Cyclase 1 / immunology
  • Antineoplastic Agents, Immunological / immunology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • B-Cell Maturation Antigen / antagonists & inhibitors
  • B-Cell Maturation Antigen / immunology
  • Humans
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / immunology
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / immunology
  • Multiple Myeloma / pathology
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / immunology
  • Signaling Lymphocytic Activation Molecule Family / antagonists & inhibitors
  • Signaling Lymphocytic Activation Molecule Family / immunology

Substances

  • Antineoplastic Agents, Immunological
  • B-Cell Maturation Antigen
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • SLAMF7 protein, human
  • Signaling Lymphocytic Activation Molecule Family
  • TNFRSF17 protein, human
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1