Omacetaxine mepesuccinate in patients with advanced chronic myeloid leukemia with resistance or intolerance to tyrosine kinase inhibitors

Abstract

Omacetaxine mepesuccinate promotes apoptosis by inhibiting the production of short-lived oncoproteins. The efficacy and safety of omacetaxine in patients with advanced chronic myeloid leukemia (CML) previously treated with tyrosine kinase inhibitors were assessed in two phase II trials (CML-202 and CML-203). Fifty-one patients in accelerated phase (AP-CML) and 44 in myeloid blast phase (BP-CML) received subcutaneous omacetaxine 1.25 mg/m² twice daily days 1–14 every 28 days until hematologic response/improvement or any cytogenetic response, then days 1–7 every 28 days until disease progression. The primary endpoint was maintenance or attainment of a major hematologic response (MHR). Cytogenetic responses were also evaluated. MHR was 37% in patients with AP-CML and 9% with BP-CML (22% and 5% in those with a history of T315I). Most grade 3/4 adverse events were related to myelosuppression, and were generally manageable. Omacetaxine demonstrates activity and an acceptable safety profile in pretreated patients with advanced CML, irrespective of mutational status.

Keywords::

• Drug resistance
• myeloid leukemias and dysplasias
• pharmacotherapeutics
• omacetaxine
• accelerated
• blast

Acknowledgements

We thank Ada Ao-Baslock, PhD, of Powered 4 Significance for her medical writing and editorial assistance.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This analysis was sponsored and funded by Teva Branded Pharmaceutical Products R&D, Inc. (TEVA). The development and publication of this manuscript has been financially supported by TEVA. Employees of TEVA were actively involved in the development of the manuscript, including providing data as well as review and comment of manuscript drafts.