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Author Notes:

E-mail Address : jcortes@mdanderson.org.

The authors thank the investigators in the Omacetaxine-202 and -203 Study Groups: Sikander Ailawadhi, Maria Baer, Charles Chuah, Valérie Coiteux, Dan Douer, Robert Emmons, Gabriel Etienne, Thierry Facon, Agnès Guerci, François Guilhot, Andrzej Hellmann, Françoise Huguet-Rigal, Pierre Laneuville, Philipp Le Coutre, Laurence Legros, Armin Leitner, Frédéric Maloisel, David Marin, Tomas Masszi, Purvish Parikh, Delphine Réa, Candido Rivera, Philippe Rousselot, Lydia Roy, Richard Van Etten, Krzysztof Warzocha, and Peter Wiernik; Dan Jones for his critical review of the manuscript; Peter Brown, DPhil, of Teva Pharmaceuticals for his critical review of the data and manuscript; and Glen Davis of Teva Pharmaceuticals for his support with collection and review of additional clinical data.

J. Cortes received research support from Novartis, BMS, Pfizer, Ariad, Deciphera, and ChemGenex, and served as a consultant for Novartis, BMS, Pfizer, Ariad, and Teva; F.E. Nicolini received research support from Novartis, received honoraria from Novartis, Ariad, BMS, and Pfizer, and served as a consultant for Novartis and Ariad; M. Wetzler received research funding, honoraria, and served as a consultant for ChemGenex and Teva; J.H. Lipton served as a consultant for Teva; L. Akard received research funding from ChemGenex, Novartis, and Pfizer, and received honoraria from Novartis, BMS, and Celgene; A. Craig, N. Nanda, and A.-C. Benichou were employed by ChemGenex and consulted for Teva; J. Leonoudakis provided medical writing assistance in the production of the manuscript, funded by Teva; H.J. Khoury received research funding from Novartis, BMS, Pfizer, Ariad, Deciphera, and ChemGenex; A. Hochhaus received research funding from and served as a consultant for ChemGenex, Novartis, BMS, MSD, Ariad, and Pfizer; M. Baccarani served as a consultant for Novartis, BMS, and Pfizer; and H.M. Kantarjian received research support from ChemGenex.

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Research Funding:

This study was sponsored by ChemGenex Pharmaceuticals, an indirect wholly owned subsidiary of Teva Pharmaceutical Industries Ltd.

Financial support for medical editorial assistance was provided by Teva Pharmaceutical Industries Ltd.

Dr. Cortes’ participation in this study was supported in part by MD Anderson Cancer Center Support Grant CA016672 and Award Number P01 CA049639 from the National Cancer Institute.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Hematology
  • Dasatinib
  • Homoharringtonine
  • Intolerance
  • Nilotinib
  • Resistance
  • CHRONIC MYELOGENOUS LEUKEMIA
  • DIAGNOSED CHRONIC-PHASE
  • CHROMOSOME-POSITIVE LEUKEMIAS
  • DURABLE CYTOGENETIC RESPONSES
  • BCR-ABL
  • FOLLOW-UP
  • THERAPY FAILURE
  • RESISTANT CML
  • END-POINT
  • DASATINIB

Subcutaneous Omacetaxine Mepesuccinate in Patients With Chronic-Phase Chronic Myeloid Leukemia Previously Treated With 2 or More Tyrosine Kinase Inhibitors Including Imatinib

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Journal Title:

Clinical Lymphoma, Myeloma and Leukemia

Volume:

Volume 13, Number 5

Publisher:

, Pages 584-591

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Introduction: Omacetaxine mepesuccinate (omacetaxine) is a first-in-class cephalotaxine that has demonstrated efficacy in CML. In this analysis we evaluated omacetaxine in CML patients with resistance or intolerance to 2 or more tyrosine kinase inhibitors (TKIs). Patients and Methods: Data were pooled from 2 phase II trials of subcutaneous omacetaxine, administered at 1.25 mg/m2 twice daily for 14 consecutive days every 28 days until response, then for 7 days every 28 days as maintenance. Patients with resistance or intolerance to imatinib and at least 1 other approved TKI (dasatinib and/or nilotinib) were included; results for patients in chronic phase (CP) are reported here. Major cytogenetic response (MCyR) was the primary end point. Results: Eighty-one patients with CML-CP (median age, 59 years; range, 26-83 years) were included in the analysis. All patients previously received imatinib, 69 (85%) previously received dasatinib, and 48 (59%) previously received nilotinib. Median omacetaxine exposure was 7.5 months (range, 0.03-38.6 months), with 13 patients ongoing. MCyR was reported in 16 patients (20%; one-sided 95% lower confidence limit, 12.8%), including 8 complete responses; median duration was 17.7 months (95% confidence interval, 4.1 months - not reached). Fifty-six patients (69%) achieved and/or maintained hematologic response for at least 8 weeks; median duration was 12.2 months (range, 8.4-26.2 months). Median failure-free and overall survival were 9.6 months and 34 months, respectively. Toxicity was mainly hematologic: the most common grade 3/4 adverse events were thrombocytopenia (67%), neutropenia (47%), and anemia (37%). Conclusion: Omacetaxine produced clinically meaningful responses with acceptable tolerability in patients with CML-CP previously treated with 2 or more TKIs.

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© 2013 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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