Phase 2 Study of Subcutaneous Omacetaxine Mepesuccinate After TKI Failure in Patients With Chronic-Phase CML With T315I Mutation

2012 Aug 15;[Epub Ahead of Print], J Cortes, JH Lipton, D Rea, R Digumarti, C Chuah, N Nanda, AC Benichou, AR Craig, M Michallet, FE Nicolini, H Kantarjian

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Results of this phase II trial of 62 patients with T3151-mutated CML who failed previous TKI therapy showed that the protein synthesis inhibitor omacetaxine mepesuccinate potentially offers safe and effective therapy for those with limited options.

Abstract
Chronic myeloid leukemia (CML) patients with the BCR-ABL T315I mutation do not benefit from therapy with currently approved tyrosine kinase inhibitors (TKIs). Omacetaxine mepesuccinate is a protein synthesis inhibitor that has demonstrated activity in cells harboring the T315I mutation. This phase 2 trial assessed the efficacy of omacetaxine in CML patients with T315I and TKI failure. Patients received subcutaneous omacetaxine 1.25 mg/m2 twice daily days 1-14 every 28 days until hematologic response or a maximum of 6 cycles, and then days 1-7 every 28 days as maintenance. Results for patients treated in chronic phase are reported here. Patients (n=62) received a median of 7 (range 1-41) cycles. Complete hematologic response was achieved in 48 patients (77%; 95% lower confidence limit [LCL], 65%); median response duration was 9.1 months. Fourteen patients (23%; 95% LCL, 13%) achieved major cytogenetic response, including complete cytogenetic response in 10 (16%). Median progression free-survival was 7.7 months. Grade 3/4 hematologic toxicity included thrombocytopenia (76%), neutropenia (44%), and anemia (39%) and was typically manageable by dose reduction. Nonhematologic adverse events were mostly grade 1/2 and included infection (42%), diarrhea (40%), and nausea (34%). Omacetaxine may provide a safe and effective treatment for CML patients with T315I mutation.

http://www.oncologystat.com/journals/journal_scans/Phase_2_Study_of_Subc...