Proteasome inhibitors for the treatment of multiple myeloma

Expert Opin Pharmacother. 2018 Mar;19(4):375-386. doi: 10.1080/14656566.2018.1441287. Epub 2018 Feb 26.

Abstract

Introduction: Multiple Myeloma (MM) management is rapidly evolving, with a spectrum of novel treatments that have changed our approach to the therapy. Proteasome inhibitors (PIs) have revolutionized the scenario of both relapsed/refractory and newly diagnosed patients. The efficacy of bortezomib, the first PI approved, followed by carfilzomib and, the oral ixazomib, have been tested in several trials as single agents or in combination.

Areas covered: In this review, the authors summarize mechanism of action, efficacy and safety of proteasome inhibitors in MM and focus on data derived from clinical trials, analyzing adverse events and their relative management.

Expert opinion: The authors believe that, currently, the best course of action in the treatment of MM is to use PIs in combination with immunomodulatory drugs (IMiDs) and/or with monoclonal antibodies for all patients. However, based on the patient-specific characteristics, it is important to avoid inappropriate discontinuation by knowing the single side effects of every agent in order to balance their efficacy and safety.

Keywords: Bortezomib; carfilzomib; ixazomib; multiple myeloma; proteasome inhibitors.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Boron Compounds / adverse effects
  • Boron Compounds / therapeutic use
  • Bortezomib / adverse effects
  • Bortezomib / therapeutic use
  • Glycine / adverse effects
  • Glycine / analogs & derivatives
  • Glycine / therapeutic use
  • Hematologic Diseases / etiology
  • Humans
  • Lactones / adverse effects
  • Lactones / therapeutic use
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism
  • Multiple Myeloma / pathology
  • Neoplasm Recurrence, Local
  • Oligopeptides / adverse effects
  • Oligopeptides / therapeutic use
  • Proteasome Inhibitors / adverse effects
  • Proteasome Inhibitors / therapeutic use*
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Boron Compounds
  • Lactones
  • Oligopeptides
  • Proteasome Inhibitors
  • Pyrroles
  • Bortezomib
  • marizomib
  • ixazomib
  • carfilzomib
  • Glycine