Investigational agents in immunotherapy: a new horizon for the treatment of multiple myeloma

Br J Haematol. 2018 May;181(4):433-446. doi: 10.1111/bjh.15116. Epub 2018 May 10.

Abstract

The treatment of multiple myeloma (MM) has gone through several major advances over the last 5 years with the introduction of next generation proteasome inhibitors (PI; carfilzomib, ixazomib) and immunomodulatory derivatives (IMiD; pomalidomide), with these new agents having a substantial impact on patient outcome. However, despite these advances, MM remains a highly resistant disease given its propensity for clonal heterogeneity and its complex interaction with the surrounding bone marrow microenvironment. Almost all patients eventually relapse despite therapeutic responses to a PI, IMiD or both. With the regulatory approval of the monoclonal antibodies Daratumumab and Elotuzumab in 2015, impressive and durable responses are being observed, even in heavily pre-treated patients who have exhausted other therapeutic options, suggesting immunological approaches in this setting have real merit. This review will focus on newer monoclonal antibodies and chimeric-antigen receptor (CAR) T cell strategies currently under investigation and in various stages of clinical development.

Keywords: BCMA; Isatuximab; Siltuximab; monoclonal antibodies; multiple myeloma.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • Humans
  • Immunologic Factors / therapeutic use*
  • Immunotherapy*
  • Multiple Myeloma / immunology
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy*
  • Proteasome Inhibitors / therapeutic use*
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / immunology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunologic Factors
  • Proteasome Inhibitors
  • elotuzumab
  • daratumumab