Daratumumab in multiple myeloma

Cancer. 2019 Jul 15;125(14):2364-2382. doi: 10.1002/cncr.32065. Epub 2019 Apr 5.

Abstract

The development of effective monoclonal antibodies for the treatment of myeloma has been a long journey of clinical and drug development. Identification of the right target antigen was a critical part of the process. CD38 as a target has been considered for some time, but clinically, daratumumab, a CD38 monoclonal antibody, was the first to be tested, and it has delivered the best clinical responses as a single agent to date. Its proven safety and efficacy in combination with other antimyeloma agents have led to several US Food and Drug Administration approvals for treating myeloma. Furthermore, the results of early trials in the induction therapy setting have demonstrated a beneficial role when it is added to the existing induction regimens. This review summarizes the importance of CD38 as a target and examines the clinical development of the CD38 monoclonal antibody daratumumab and its clinical significance in combination regimens in both patients with relapsed/refractory myeloma and patients with newly diagnosed myeloma.

Keywords: CD38 monoclonal antibody; daratumumab; infusion reactions; myeloma; myeloma management.

Publication types

  • Review

MeSH terms

  • ADP-ribosyl Cyclase 1 / immunology
  • ADP-ribosyl Cyclase 1 / metabolism
  • Amyloidosis / drug therapy
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Evaluation, Preclinical
  • Drug Resistance, Neoplasm
  • Humans
  • Immunotherapy / methods
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality*
  • Survival Rate
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • Membrane Glycoproteins
  • daratumumab
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1