Subcutaneous omacetaxine mepesuccinate in patients with chronic-phase chronic myeloid leukemia previously treated with 2 or more tyrosine kinase inhibitors including imatinib

Jorge E. Cortes, Franck E. Nicolini, Meir Wetzler, Jeffrey H. Lipton, Luke Akard, Adam Craig, Nisha Nanda, Annie Claude Benichou, Janis Leonoudakis, H. Jean Khoury, Andreas Hochhaus, Michele Baccarani, Hagop M. Kantarjian

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)584-591
Number of pages8
JournalClinical Lymphoma, Myeloma and Leukemia
Volume13
Issue number5
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Protein-Tyrosine Kinases
Cytogenetics
Imatinib Mesylate
homoharringtonine
Neutropenia
Thrombocytopenia
Anemia
Maintenance
Confidence Intervals

Keywords

  • Dasatinib
  • Homoharringtonine
  • Intolerance
  • Nilotinib
  • Resistance

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Subcutaneous omacetaxine mepesuccinate in patients with chronic-phase chronic myeloid leukemia previously treated with 2 or more tyrosine kinase inhibitors including imatinib. / Cortes, Jorge E.; Nicolini, Franck E.; Wetzler, Meir; Lipton, Jeffrey H.; Akard, Luke; Craig, Adam; Nanda, Nisha; Benichou, Annie Claude; Leonoudakis, Janis; Khoury, H. Jean; Hochhaus, Andreas; Baccarani, Michele; Kantarjian, Hagop M.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 13, No. 5, 01.10.2013, p. 584-591.

Research output: Contribution to journalArticle

Cortes, JE, Nicolini, FE, Wetzler, M, Lipton, JH, Akard, L, Craig, A, Nanda, N, Benichou, AC, Leonoudakis, J, Khoury, HJ, Hochhaus, A, Baccarani, M & Kantarjian, HM 2013, 'Subcutaneous omacetaxine mepesuccinate in patients with chronic-phase chronic myeloid leukemia previously treated with 2 or more tyrosine kinase inhibitors including imatinib', Clinical Lymphoma, Myeloma and Leukemia, vol. 13, no. 5, pp. 584-591. https://doi.org/10.1016/j.clml.2013.03.020
Cortes, Jorge E. ; Nicolini, Franck E. ; Wetzler, Meir ; Lipton, Jeffrey H. ; Akard, Luke ; Craig, Adam ; Nanda, Nisha ; Benichou, Annie Claude ; Leonoudakis, Janis ; Khoury, H. Jean ; Hochhaus, Andreas ; Baccarani, Michele ; Kantarjian, Hagop M. / Subcutaneous omacetaxine mepesuccinate in patients with chronic-phase chronic myeloid leukemia previously treated with 2 or more tyrosine kinase inhibitors including imatinib. In: Clinical Lymphoma, Myeloma and Leukemia. 2013 ; Vol. 13, No. 5. pp. 584-591.
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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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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.

PY - 2013/10/1

Y1 - 2013/10/1

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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