A phase II study of omacetaxine mepesuccinate for patients with higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia after failure of hypomethylating agents

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Abstract

The outcome of patients with myelodysplastic syndromes (MDSs) after failure of hypomethylating agents (HMAs) failure is poor with a median overall survival (OS) of only 4-6 months. Omacetaxine mepesuccinate (OM) is safe and effective in myeloid malignancies but has not been studied in MDS with HMA failure. We conducted a phase II study of OM in patients with MDS or chronic myelomonocytic leukemia (CMML) who had previously failed or been intolerant to HMAs. Patients received OM at a dose of 1.25 mg/m2 subcutaneously every 12 hours for 3 consecutive days on a 4- to 7-week schedule. The primary endpoints were the overall response rate (ORR) and OS. A total of 42 patients were enrolled with a median age of 76 years. The ORR was 33%. Patients with diploid cytogenetics were more likely to respond to OM than were those with cytogenetic abnormalities (58% vs 23%, respectively; P =.03). Overall, the median OS was 7.5 months and 1-year OS rate was 25%. Patients with diploid cytogenetics had superior OS to those with cytogenetic abnormalities (median OS 14.8 vs 6.8 months, respectively; P =.01). Two patients had ongoing response to OM of 2 years or longer (both MDS with diploid cytogenetics and RUNX1 mutation). The most common grade ≥ 3 adverse events were infections in 11 patients (26%), febrile neutropenia in 4 (10%), and hemorrhage in 3 (7%). Overall, OM was safe and active in patients with MDS or CMML who experienced HMA failure. These results support the further development of OM in this setting.

Original languageEnglish (US)
Pages (from-to)74-79
Number of pages6
JournalAmerican journal of hematology
Volume94
Issue number1
DOIs
StatePublished - Jan 1 2019

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Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Diploidy
Cytogenetics
Survival
Chromosome Aberrations
Survival Rate
homoharringtonine
Febrile Neutropenia
Appointments and Schedules
Hemorrhage

ASJC Scopus subject areas

  • Hematology

Cite this

@article{244bce026fac455b9fde42b63e017d68,
title = "A phase II study of omacetaxine mepesuccinate for patients with higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia after failure of hypomethylating agents",
abstract = "The outcome of patients with myelodysplastic syndromes (MDSs) after failure of hypomethylating agents (HMAs) failure is poor with a median overall survival (OS) of only 4-6 months. Omacetaxine mepesuccinate (OM) is safe and effective in myeloid malignancies but has not been studied in MDS with HMA failure. We conducted a phase II study of OM in patients with MDS or chronic myelomonocytic leukemia (CMML) who had previously failed or been intolerant to HMAs. Patients received OM at a dose of 1.25 mg/m2 subcutaneously every 12 hours for 3 consecutive days on a 4- to 7-week schedule. The primary endpoints were the overall response rate (ORR) and OS. A total of 42 patients were enrolled with a median age of 76 years. The ORR was 33{\%}. Patients with diploid cytogenetics were more likely to respond to OM than were those with cytogenetic abnormalities (58{\%} vs 23{\%}, respectively; P =.03). Overall, the median OS was 7.5 months and 1-year OS rate was 25{\%}. Patients with diploid cytogenetics had superior OS to those with cytogenetic abnormalities (median OS 14.8 vs 6.8 months, respectively; P =.01). Two patients had ongoing response to OM of 2 years or longer (both MDS with diploid cytogenetics and RUNX1 mutation). The most common grade ≥ 3 adverse events were infections in 11 patients (26{\%}), febrile neutropenia in 4 (10{\%}), and hemorrhage in 3 (7{\%}). Overall, OM was safe and active in patients with MDS or CMML who experienced HMA failure. These results support the further development of OM in this setting.",
author = "Short, {Nicholas J} and Jabbour, {Elias Joseph} and Kiran Naqvi and Ami Patel and Jing Ning and Koji Sasaki and Nogueras-Gonzalez, {Graciela M.} and Prithviraj Bose and Kornblau, {Steven M} and Koichi Takahashi and Michael Andreeff and Gabriela Sanchez-Petitto and Zeev Estrov and Courtney DiNardo and {Montalban Bravo}, Guillermo and Marina Konopleva and Yesid Alvarado and Kapil Bhalla and Fiskus, {Warren C} and Maria Khouri and Rubiul Islam and Kantarjian, {Hagop M} and Guillermo Garcia-Manero",
year = "2019",
month = "1",
day = "1",
doi = "10.1002/ajh.25318",
language = "English (US)",
volume = "94",
pages = "74--79",
journal = "American Journal of Hematology",
issn = "0361-8609",
publisher = "Wiley-Liss Inc.",
number = "1",

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TY - JOUR

T1 - A phase II study of omacetaxine mepesuccinate for patients with higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia after failure of hypomethylating agents

AU - Short, Nicholas J

AU - Jabbour, Elias Joseph

AU - Naqvi, Kiran

AU - Patel, Ami

AU - Ning, Jing

AU - Sasaki, Koji

AU - Nogueras-Gonzalez, Graciela M.

AU - Bose, Prithviraj

AU - Kornblau, Steven M

AU - Takahashi, Koichi

AU - Andreeff, Michael

AU - Sanchez-Petitto, Gabriela

AU - Estrov, Zeev

AU - DiNardo, Courtney

AU - Montalban Bravo, Guillermo

AU - Konopleva, Marina

AU - Alvarado, Yesid

AU - Bhalla, Kapil

AU - Fiskus, Warren C

AU - Khouri, Maria

AU - Islam, Rubiul

AU - Kantarjian, Hagop M

AU - Garcia-Manero, Guillermo

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The outcome of patients with myelodysplastic syndromes (MDSs) after failure of hypomethylating agents (HMAs) failure is poor with a median overall survival (OS) of only 4-6 months. Omacetaxine mepesuccinate (OM) is safe and effective in myeloid malignancies but has not been studied in MDS with HMA failure. We conducted a phase II study of OM in patients with MDS or chronic myelomonocytic leukemia (CMML) who had previously failed or been intolerant to HMAs. Patients received OM at a dose of 1.25 mg/m2 subcutaneously every 12 hours for 3 consecutive days on a 4- to 7-week schedule. The primary endpoints were the overall response rate (ORR) and OS. A total of 42 patients were enrolled with a median age of 76 years. The ORR was 33%. Patients with diploid cytogenetics were more likely to respond to OM than were those with cytogenetic abnormalities (58% vs 23%, respectively; P =.03). Overall, the median OS was 7.5 months and 1-year OS rate was 25%. Patients with diploid cytogenetics had superior OS to those with cytogenetic abnormalities (median OS 14.8 vs 6.8 months, respectively; P =.01). Two patients had ongoing response to OM of 2 years or longer (both MDS with diploid cytogenetics and RUNX1 mutation). The most common grade ≥ 3 adverse events were infections in 11 patients (26%), febrile neutropenia in 4 (10%), and hemorrhage in 3 (7%). Overall, OM was safe and active in patients with MDS or CMML who experienced HMA failure. These results support the further development of OM in this setting.

AB - The outcome of patients with myelodysplastic syndromes (MDSs) after failure of hypomethylating agents (HMAs) failure is poor with a median overall survival (OS) of only 4-6 months. Omacetaxine mepesuccinate (OM) is safe and effective in myeloid malignancies but has not been studied in MDS with HMA failure. We conducted a phase II study of OM in patients with MDS or chronic myelomonocytic leukemia (CMML) who had previously failed or been intolerant to HMAs. Patients received OM at a dose of 1.25 mg/m2 subcutaneously every 12 hours for 3 consecutive days on a 4- to 7-week schedule. The primary endpoints were the overall response rate (ORR) and OS. A total of 42 patients were enrolled with a median age of 76 years. The ORR was 33%. Patients with diploid cytogenetics were more likely to respond to OM than were those with cytogenetic abnormalities (58% vs 23%, respectively; P =.03). Overall, the median OS was 7.5 months and 1-year OS rate was 25%. Patients with diploid cytogenetics had superior OS to those with cytogenetic abnormalities (median OS 14.8 vs 6.8 months, respectively; P =.01). Two patients had ongoing response to OM of 2 years or longer (both MDS with diploid cytogenetics and RUNX1 mutation). The most common grade ≥ 3 adverse events were infections in 11 patients (26%), febrile neutropenia in 4 (10%), and hemorrhage in 3 (7%). Overall, OM was safe and active in patients with MDS or CMML who experienced HMA failure. These results support the further development of OM in this setting.

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DO - 10.1002/ajh.25318

M3 - Article

VL - 94

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JF - American Journal of Hematology

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