Immunopathogenesis and immunotherapy of multiple myeloma

Int J Hematol. 2018 Mar;107(3):278-285. doi: 10.1007/s12185-018-2405-7. Epub 2018 Jan 24.

Abstract

Despite the advent of novel therapies and improvements in survival, multiple myeloma (MM) remains an incurable disease. Thus, new treatment strategies including immunotherapies are needed for MM patients with stable disease after induction chemotherapy as well as for disease control in patients with advanced disease. However, profound immune dysregulation not only of B cells, but also of other immune cells such as natural killer cells, T cells, and dendritic cells and increase in the number of immunosuppressive cells, i.e., regulatory T and B cells and myeloid-derived suppressor cells, have been demonstrated in advanced MM patients, which may be involved in disease progression. Because of immune dysfunction, immunotherapies have not shown clinical efficacy in MM patients. It is therefore crucial to resolve immunosuppressive mechanisms and improve immune responses, especially in advanced MM patients. Recently, excellent clinical efficacy of new immunotherapeutic strategies such as immunomodulatory drug-intensified monoclonal antibody treatment, immune checkpoint inhibitors, and chimeric antigen receptor T-cell therapy targeting B cell maturation antigen has been reported in advanced-stage MM patients. Those new treatments or their combination will improve prognosis and possibly point toward a cure for myeloma.

Keywords: Chimeric antigen receptor T-cell therapy; Immune checkpoint inhibitor; Immunomodulatory drug; Immunotherapy; Multiple myeloma.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • B-Lymphocytes / immunology
  • B-Lymphocytes, Regulatory / immunology
  • Combined Modality Therapy
  • Dendritic Cells / immunology
  • Disease Progression
  • Humans
  • Immune Tolerance
  • Immunologic Factors / therapeutic use
  • Immunotherapy* / methods
  • Immunotherapy* / trends
  • Induction Chemotherapy
  • Killer Cells, Natural / immunology
  • Molecular Targeted Therapy
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / therapy*
  • Prognosis
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Antibodies, Monoclonal
  • Immunologic Factors