Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus

N Engl J Med. 2020 Sep 17;383(12):1149-1155. doi: 10.1056/NEJMoa2023325.

Abstract

Daratumumab, a human monoclonal antibody that targets CD38, depletes plasma cells and is approved for the treatment of multiple myeloma. Long-lived plasma cells are implicated in the pathogenesis of systemic lupus erythematosus because they secrete autoantibodies, but they are unresponsive to standard immunosuppression. We describe the use of daratumumab that induced substantial clinical responses in two patients with life-threatening lupus, with the clinical responses sustained by maintenance therapy with belimumab, an antibody to B-cell activating factor. Significant depletion of long-lived plasma cells, reduction of interferon type I activity, and down-regulation of T-cell transcripts associated with chronic inflammation were documented. (Supported by the Deutsche Forschungsgemeinschaft and others.).

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / antagonists & inhibitors*
  • ADP-ribosyl Cyclase 1 / metabolism
  • Adult
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Creatinine / blood
  • Creatinine / urine
  • Down-Regulation
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Interferon Type I / antagonists & inhibitors
  • Lupus Erythematosus, Systemic / drug therapy*
  • Maintenance Chemotherapy
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Plasma Cells / drug effects*
  • Proteinuria
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunosuppressive Agents
  • Interferon Type I
  • Membrane Glycoproteins
  • daratumumab
  • belimumab
  • Creatinine
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1