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

J. Cortes, R. Digumarti, P. M. Parikh, M. Wetzler, J. H. Lipton, A. Hochhaus, A. R. Craig, A. C. Benichou, F. E. Nicolini, H. M. Kantarjian

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)350-354
Number of pages5
JournalAmerican Journal of Hematology
Volume88
Issue number5
DOIs
StatePublished - May 1 2013
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Hematology

Cite this

Cortes, J., Digumarti, R., Parikh, P. M., Wetzler, M., Lipton, J. H., Hochhaus, A., Craig, A. R., Benichou, A. C., Nicolini, F. E., & Kantarjian, H. M. (2013). Phase 2 study of subcutaneous omacetaxine mepesuccinate for chronic-phase chronic myeloid leukemia patients resistant to or intolerant of tyrosine kinase inhibitors. American Journal of Hematology, 88(5), 350-354. https://doi.org/10.1002/ajh.23408