A safety evaluation of omacetaxine mepesuccinate for the treatment of chronic myeloid leukemia

Expert Opin Drug Saf. 2016 Sep;15(9):1279-86. doi: 10.1080/14740338.2016.1207760. Epub 2016 Jul 15.


Introduction: Therapy of chronic myeloid leukemia (CML) has been completely transformed by the development of tyrosine kinase inhibitors (TKIs). However, a subset of patients will fail TKI therapy due to resistance or intolerance. Omacetaxine mepesuccinate (OM), a protein translation inhibitor, is currently the only approved therapy that does not directly target the kinase domain. It has activity for CML patients irrespective of the phase or underlying kinase domain mutation status.

Areas covered: We searched the MEDLINE database for articles published in English on homoharringtonine or omacetaxine from 1970 to present. This article reviews the pharmacokinetics of OM and its clinical evolution for the treatment of CML pre- and post TKI development. Toxicity profile, drug administration and future directions are also discussed.

Expert opinion: OM represents a unique addition to the CML therapeutic armamentarium with its distinct mechanism of action and activity. The adverse event profile is manageable and with subcutaneous administration at the approved dose, cardiac toxicity is no longer a concern. The recent approval of home administration will facilitate access to this therapy and increase patient compliance. We conclude with specific scenarios where OM use should be considered in CP and AP-CML patients in the era of TKI therapy.

Keywords: Chronic myelogenous leukemia; T315I mutation; omacetaxine mepesuccinate; tyrosine kinase inhibitor.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / pharmacokinetics
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Drug Resistance, Neoplasm
  • Harringtonines / adverse effects
  • Harringtonines / pharmacokinetics
  • Harringtonines / therapeutic use*
  • Homoharringtonine
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Protein Kinase Inhibitors / therapeutic use


  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Phytogenic
  • Harringtonines
  • Protein Kinase Inhibitors
  • Homoharringtonine