TY - JOUR
T1 - Subcutaneous omacetaxine mepesuccinate in patients with chronic-phase chronic myeloid leukemia previously treated with 2 or more tyrosine kinase inhibitors including imatinib
AU - Cortes, Jorge E.
AU - Nicolini, Franck E.
AU - Wetzler, Meir
AU - Lipton, Jeffrey H.
AU - Akard, Luke
AU - Craig, Adam
AU - Nanda, Nisha
AU - Benichou, Annie Claude
AU - Leonoudakis, Janis
AU - Khoury, H. Jean
AU - Hochhaus, Andreas
AU - Baccarani, Michele
AU - Kantarjian, Hagop M.
N1 - Funding Information:
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.
Funding Information:
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.
PY - 2013/10
Y1 - 2013/10
N2 - 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.
AB - 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.
KW - Dasatinib
KW - Homoharringtonine
KW - Intolerance
KW - Nilotinib
KW - Resistance
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U2 - 10.1016/j.clml.2013.03.020
DO - 10.1016/j.clml.2013.03.020
M3 - Article
C2 - 23787123
AN - SCOPUS:84884146561
SN - 2152-2650
VL - 13
SP - 584
EP - 591
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 5
ER -