Phase 2 study of subcutaneous omacetaxine mepesuccinate for chronic‐phase chronic myeloid leukemia patients resistant to or intolerant of tyrosine kinase inhibitors

Omacetaxine mepesuccinate (omacetaxine) is a first‐in‐class cephalotaxine with a unique mode of action, independent of BCR‐ABL, that has shown promising activity in patients with chronic myeloid leukemia (CML). This multicenter, noncomparative, open‐label phase 2 study evaluated the efficacy and safety of subcutaneous omacetaxine in CML patients with resistance or intolerance to two or more tyrosine kinase inhibitors (TKIs); results in patients in chronic phase are reported here. Patients received subcutaneous omacetaxine 1.25 mg/m2 twice daily days 1–14 every 28 days until hematologic response (up to a maximum of six cycles), then days 1–7 every 28 days as maintenance. Primary endpoints were rates of hematologic response lasting >8 weeks and major cytogenetic response (MCyR). Forty‐six patients were enrolled: all had received imatinib, 83% had received dasatinib, and 57% nilotinib. A median 4.5 cycles of omacetaxine were administered (range, 1–36). Hematologic response was achieved or maintained in 31 patients (67%); median response duration was 7.0 months. Ten patients (22%) achieved MCyR, including 2 (4%) complete cytogenetic responses. Median progression‐free survival was 7.0 months [95% confidence interval (CI), 5.9–8.9 months], and overall survival was 30.1 months (95% CI, 20.3 months—not reached). Grade 3/4 hematologic toxicity included thrombocytopenia (54%), neutropenia (48%), and anemia (33%). Nonhematologic adverse events were predominantly grade 1/2 and included diarrhea (44%), nausea (30%), fatigue (24%), pyrexia (20%), headache (20%), and asthenia (20%). Subcutaneous omacetaxine may offer clinical benefit to patients with chronic‐phase CML with resistance or intolerance to multiple TKI therapies. Am. J. Hematol. 88:350–354, 2013. © 2013 Wiley Periodicals, Inc.