CD38-targeting antibodies in multiple myeloma: mechanisms of action and clinical experience

Expert Rev Clin Immunol. 2018 Mar;14(3):197-206. doi: 10.1080/1744666X.2018.1443809. Epub 2018 Feb 28.

Abstract

Multiple myeloma (MM) is generally an incurable hematological malignancy with heterogeneous overall survival rates ranging from a few months to more than 10 years. Survival is especially poor for patients who developed disease that is refractory to immunomodulatory drugs and proteasome inhibitors. Areas covered: This review will discuss the importance of CD38-targeting antibodies for the treatment of MM patients to improve their outcome. Expert commentary: Intense immuno-oncological laboratory research has resulted in the development of functionally active monoclonal antibodies against cell surface markers present on MM cells. In this respect, CD38-targeting antibodies such as daratumumab, MOR202, and isatuximab, have high single agent activity in heavily pretreated MM patients by virtue of their pleiotropic mechanisms of action including Fc-dependent effector mechanisms and immunomodulatory activities. Importantly, CD38-targeting antibodies are well tolerated, with infusion reactions as most frequent adverse event. Altogether, this makes them attractive combination partners with other anti-MM agents. Daratumumab is already approved as monotherapy and in combination with lenalidomide-dexamethasone as well as bortezomib-dexamethasone in pretreated MM patients. Furthermore, results from studies evaluating CD38-targeting antibodies in newly diagnosed MM patients are also promising, indicating that CD38-targeting antibodies will be broadly used in MM, resulting in further improvements in survival.

Keywords: CD38 antibodies; MOR202; TAK-079; daratumumab; immunotherapy; isatuximab; multiple myeloma; smoldering myeloma.

Publication types

  • Review

MeSH terms

  • ADP-ribosyl Cyclase 1 / immunology*
  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm / immunology*
  • Dexamethasone / therapeutic use
  • Drug Therapy, Combination
  • Humans
  • Immunotherapy / methods*
  • Injection Site Reaction
  • Molecular Targeted Therapy
  • Multiple Myeloma / immunology
  • Multiple Myeloma / mortality
  • Multiple Myeloma / therapy*
  • Patient Outcome Assessment
  • Survival Analysis

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, Neoplasm
  • daratumumab
  • Dexamethasone
  • ADP-ribosyl Cyclase 1
  • isatuximab