Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic- or accelerated-phase chronic myeloid leukemia: Results with 24 months of follow-up

Jorge E. Cortes, Hagop M. Kantarjian, Delphine Rea, Meir Wetzler, Jeffrey H. Lipton, Luke Akard, H. Jean Khoury, Mauricette Michallet, Agnès Guerci-Bresler, Charles Chuah, Andrzej Hellmann, Raghunadharao Digumarti, Purvish M. Parikh, Laurence Legros, Krzysztof Warzocha, Michele Baccarani, Elizabeth Li, Mihaela Munteanu, Franck E. Nicolini

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

BACKGROUND Omacetaxine, a protein synthesis inhibitor, is indicated in the United States for the treatment of patients with chronic-phase (CP) or accelerated-phase (AP) chronic myeloid leukemia (CML) with resistance and/or intolerance to 2 or more tyrosine kinase inhibitors. METHODS The final analysis, with 24 months of follow-up, included additional efficacy and safety analyses to assess the benefit of long-term omacetaxine administration (1.25 mg/m2 twice daily for 14 days every 28 days followed by 7 days every 28 days) in CP-CML and AP-CML patients receiving >3 cycles. RESULTS Eighteen percent of CP-CML patients achieved a major cytogenetic response (MCyR) with a median duration of 12.5 months (95% confidence interval [CI], 3.5 months to not reached [NR]); responses were maintained for ≥12 months in 3 of 14 responders, and the median overall survival (OS) was 40.3 months (95% CI, 23.8 months to NR). Among patients with AP-CML, 14% achieved or maintained a major hematologic response for a median of 4.7 months (95% CI, 3.6 months to NR); MCyR was not achieved, and the median OS was 14.3 months (95% CI, 6.7-18.7 months). In patients with CP-CML and patients with AP-CML who received >3 cycles of treatment (n = 50 and n = 14, respectively), the median OS was 49.3 months (95% CI, 23.8 months to NR) and 24.6 months (95% CI, 12-37.2 months), respectively. Grade 3 or higher hematologic toxicities were the major side effects (79% and 73% for CP-CML and AP-CML, respectively), with discontinuation due to toxicity in 10% of CP patients and in 5% of AP patients. CONCLUSIONS These results suggest that the long-term administration of omacetaxine is feasible with dose adjustments to manage toxicities and that omacetaxine provides a durable benefit for some patients. Cancer 2015;121:1637-1644.

Original languageEnglish (US)
Pages (from-to)1637-1644
Number of pages8
JournalCancer
Volume121
Issue number10
DOIs
StatePublished - May 1 2015
Externally publishedYes

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Keywords

  • T315I
  • intolerance
  • protein synthesis inhibitor
  • resistance
  • tyrosine kinase inhibitor (TKI)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cortes, J. E., Kantarjian, H. M., Rea, D., Wetzler, M., Lipton, J. H., Akard, L., Khoury, H. J., Michallet, M., Guerci-Bresler, A., Chuah, C., Hellmann, A., Digumarti, R., Parikh, P. M., Legros, L., Warzocha, K., Baccarani, M., Li, E., Munteanu, M., & Nicolini, F. E. (2015). Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic- or accelerated-phase chronic myeloid leukemia: Results with 24 months of follow-up. Cancer, 121(10), 1637-1644. https://doi.org/10.1002/cncr.29240