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.

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/m(2) 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.

• Authors: 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
• Journal: Cancer (Cancer) Vol. 121 Issue 10 Pg. 1637-44 (May 15 2015) ISSN: 1097-0142 [Electronic] United States
• PMID: 25586015 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Cancer Society.

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents, Phytogenic
• Harringtonines
• Protein Kinase Inhibitors
• Homoharringtonine
• Protein-Tyrosine Kinases

Topics

• Adult
• Aged
• Angiogenesis Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects, therapeutic use)
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Female
• Follow-Up Studies
• Harringtonines (administration & dosage, adverse effects, therapeutic use)
• Homoharringtonine
• Humans
• Leukemia, Myeloid, Accelerated Phase (drug therapy)
• Leukemia, Myeloid, Chronic-Phase (drug therapy)
• Male
• Middle Aged
• Protein Kinase Inhibitors (pharmacology)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Treatment Outcome