Omacetaxine mepesuccinate for management of chronic myeloid leukemia

Abstract

Introduction: Omacetaxine mepesuccinate (‘omacetaxine') is a reversible inhibitor of protein synthesis that promotes apoptosis by reducing levels of short-lived oncoproteins.

Areas covered: Unmet needs in chronic myeloid leukemia (CML), clinical development of omacetaxine and clinical activity of omacetaxine in CML.

Expert opinion: Clinical activity of omacetaxine in CML was shown in two Phase II open-label studies of patients with treatment-resistant CML: the first in patients with imatinib failure and the T315I mutation, and the second in patients with resistance to or intolerance of two or more tyrosine kinase inhibitors (TKIs). In a combined analysis, 69% (56/81) of CML chronic phase (CP) patients achieved and/or maintained hematologic response for ≥ 8 weeks. Major cytogenetic response was induced in 20%, including 10% with complete cytogenetic response. Overall, 35% of CML-CP patients had ‘any' cytogenetic response. Median overall survival was 34 months. Hematologic toxicity associated with omacetaxine is typically manageable by reducing the number of treatment days per cycle and/or delaying the start of the next treatment cycle. Omacetaxine provides a treatment option with a distinct mechanism of action for patients who have not achieved an optimal outcome with TKIs, including patients with the T315I mutation.

Keywords::

• chronic myeloid leukemia
• homoharringtonine
• omacetaxine mepesuccinate
• protein synthesis inhibitor