Subcutaneous omacetaxine mepesuccinate in chronic myeloid leukemia (CML) patients resistant or intolerant to two or more tyrosine kinase inhibitors (TKIs): Data from an ongoing phase II trial

Abstract

7027 Background: Omacetaxine (OM), a first-in-class cetaxine, shows clinical activity against Ph+ CML with a mechanism of action independent to tyrosine kinase inhibition. Patients (Pts) who have failed multiple TKIs may benefit from an alternative therapy for CML. Methods: Pts include adult CML following resistance or intolerance to at least 2 TKIs. T315I+ Pts are enrolled in a separate trial. Pts receive OM induction at 1.25 mg/m2 subcutaneous (SC) BID for 14 days every 28 days followed by maintenance at 1.25 mg/m2 SC BID for 7 days every 28 days (maintenance after at least one induction cycle and achievement of hematologic response). Results: 60 pts (30 chronic phase [CP], 14 accelerated phase [AP], and 16 blast phase [BP] have been enrolled with 51% having failed at least 3 prior TKIs. Median age: 58 yrs; 50% male. Median disease duration: 74 months. At baseline, 38.5% of pts had Bcr-Abl mutations including 9.6% with compound mutations. The most frequently observed mutations were F317L (11.5%) and V299L (5.8%). OM is well tolerated with transient myelosuppression as the primary toxicity. Grade 3/4 non-hematologic events are rare with pyrexia occurring in 4.3% of patients. Efficacy data are available for 30 Pts: Conclusions: Omacetaxine in multi-TKI resistant or intolerant CML is well tolerated and has achieved hematologic and cytogenetic responses in these heavily pre-treated Pts. [Table: see text] [Table: see text]