Omacetaxine mepesuccinate in the treatment of intractable chronic myeloid leukemia
Yaoyu Chen,1 Shaoguang Li2
1Department of Oncology, Novartis Institutes for Biomedical Research, Cambridge, 2Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA
Abstract: In a significant proportion of patients with chronic myeloid leukemia, resistance to BCR-ABL tyrosine kinase inhibitors develops due to acquisition of BCR-ABL kinase domain mutations and insensitivity of leukemia stem cells to tyrosine kinase inhibitors. Omacetaxine mepesuccinate (formerly called homoharringtonine) is a natural alkaloid that inhibits protein synthesis and induces cell death. Omacetaxine mepesuccinate has been recently approved by the US Food and Drug Administration to treat patients with chronic myeloid leukemia who failed to respond to multiple tyrosine kinase inhibitors and/or acquired the BCR-ABL-T315I mutation. In this review, we discuss the use and effectiveness of omacetaxine mepesuccinate in the treatment of chronic myeloid leukemia, with coverage of its pharmacology, mode of action, and pharmacokinetics. We believe that omacetaxine mepesuccinate will be beneficial to many patients with chronic myeloid leukemia who do not respond well to tyrosine kinase inhibitors.
Keywords: BCR-ABL, leukemic stem cells, chronic myeloid leukemia, biomarker, hematopoietic stem cells, cancer stem cells