Plitidepsin: a potential new treatment for relapsed/refractory multiple myeloma

Future Oncol. 2019 Jan;15(2):109-120. doi: 10.2217/fon-2018-0492. Epub 2018 Aug 16.

Abstract

Plitidepsin is a marine-derived anticancer compound isolated from the Mediterranean tunicate Applidium albicans. It exerts pleiotropic effects on cancer cells, most likely by binding to the eukaryotic translation eEF1A2. This ultimately leads to cell-cycle arrest, growth inhibition and induction of apoptosis via multiple pathway alterations. Recently, a Phase III randomized trial in patients with relapsed/refractory multiple myeloma reported outcomes for plitidepsin plus dexamethasone compared with dexamethasone. Median progression-free survival was 3.8 months in the plitidepsin arm and 1.9 months in the dexamethasone arm (HR: 0.611; p = 0.0048). Here, we review preclinical data regarding plitidepsins mechanism of action, give an overview of clinical trial results across different tumor types as well as the latest results in multiple myeloma.

Keywords: Aplidin; eukaryotic translation elongation factor 1 α 2; multiple myeloma; plitidepsin.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects
  • Aquatic Organisms / chemistry
  • Clinical Trials, Phase III as Topic
  • Depsipeptides / pharmacology
  • Depsipeptides / therapeutic use*
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Humans
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Peptide Elongation Factor 1 / metabolism
  • Progression-Free Survival
  • Randomized Controlled Trials as Topic
  • Urochordata / chemistry*

Substances

  • Depsipeptides
  • EEF1A2 protein, human
  • Peptide Elongation Factor 1
  • Dexamethasone
  • plitidepsin