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

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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Leukemia, Myeloid, Accelerated Phase
Safety
Leukemia, Myeloid, Chronic Phase
Confidence Intervals
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Cytogenetics
Survival
homoharringtonine
Protein Synthesis Inhibitors
Protein-Tyrosine Kinases

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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

In: Cancer, Vol. 121, No. 10, 01.05.2015, p. 1637-1644.

Research output: Contribution to journalArticle

Cortes, JE, Kantarjian, HM, Rea, D, Wetzler, M, Lipton, JH, Akard, L, Khoury, HJ, Michallet, M, Guerci-Bresler, A, Chuah, C, Hellmann, A, Digumarti, R, Parikh, PM, Legros, L, Warzocha, K, Baccarani, M, Li, E, Munteanu, M & Nicolini, FE 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, vol. 121, no. 10, pp. 1637-1644. https://doi.org/10.1002/cncr.29240
Cortes, Jorge E. ; Kantarjian, Hagop M. ; Rea, Delphine ; Wetzler, Meir ; Lipton, Jeffrey H. ; Akard, Luke ; Khoury, H. Jean ; Michallet, Mauricette ; Guerci-Bresler, Agnès ; Chuah, Charles ; Hellmann, Andrzej ; Digumarti, Raghunadharao ; Parikh, Purvish M. ; Legros, Laurence ; Warzocha, Krzysztof ; Baccarani, Michele ; Li, Elizabeth ; Munteanu, Mihaela ; Nicolini, Franck E. / 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. In: Cancer. 2015 ; Vol. 121, No. 10. pp. 1637-1644.
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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.",
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TY - JOUR

T1 - Final analysis of the efficacy and safety of omacetaxine mepesuccinate in patients with chronic- or accelerated-phase chronic myeloid leukemia

T2 - Results with 24 months of follow-up

AU - Cortes, Jorge E.

AU - Kantarjian, Hagop M.

AU - Rea, Delphine

AU - Wetzler, Meir

AU - Lipton, Jeffrey H.

AU - Akard, Luke

AU - Khoury, H. Jean

AU - Michallet, Mauricette

AU - Guerci-Bresler, Agnès

AU - Chuah, Charles

AU - Hellmann, Andrzej

AU - Digumarti, Raghunadharao

AU - Parikh, Purvish M.

AU - Legros, Laurence

AU - Warzocha, Krzysztof

AU - Baccarani, Michele

AU - Li, Elizabeth

AU - Munteanu, Mihaela

AU - Nicolini, Franck E.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

KW - intolerance

KW - protein synthesis inhibitor

KW - resistance

KW - T315I

KW - tyrosine kinase inhibitor (TKI)

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