Daratumumab for the treatment of AL amyloidosis

Leuk Lymphoma. 2019 Feb;60(2):295-301. doi: 10.1080/10428194.2018.1485914. Epub 2018 Jul 22.

Abstract

Autologous stem cell transplantation (ASCT) has been used as treatment for immunoglobulin light-chain (AL) amyloidosis for over two decades with improving outcomes; however, the majority of patients are not candidates for this therapy at diagnosis. Novel agents such as immunomodulatory drugs, proteasome inhibitors, and immunotherapy with monoclonal antibodies targeting CD38 have been adopted from the multiple myeloma spheres with encouraging results. Herein, we discuss the role of daratumumab, a monoclonal antibody to CD38, in the treatment of AL amyloidosis. We focus on its mechanism of action, tolerability, and the current published data on its use in AL amyloidosis. Early data from phase I and phase II studies show that daratumumab is tolerated well in this population and induces rapid and deep responses. Phase III trials are currently accruing and we envision daratumumab becoming a key component in the treatment of AL amyloidosis in the future.

Keywords: AL amyloidosis; CD38; Daratumumab; immunotherapy; monoclonal antibody.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADP-ribosyl Cyclase 1 / antagonists & inhibitors
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Disease Management
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Immunoglobulin Light-chain Amyloidosis / diagnosis
  • Immunoglobulin Light-chain Amyloidosis / drug therapy*
  • Immunoglobulin Light-chain Amyloidosis / etiology
  • Membrane Glycoproteins / antagonists & inhibitors
  • Molecular Targeted Therapy
  • Transplantation, Autologous
  • Treatment Outcome

Substances

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