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
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 D.
AU - Montalban-Bravo, Guillermo
AU - Konopleva, Marina
AU - Alvarado, Yesid
AU - Bhalla, Kapil N.
AU - Fiskus, Warren
AU - Khouri, Maria
AU - Islam, Rubiul
AU - Kantarjian, Hagop
AU - Garcia-Manero, Guillermo
N1 - Publisher Copyright:
© 2018 Wiley Periodicals, Inc.
PY - 2019/1
Y1 - 2019/1
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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U2 - 10.1002/ajh.25318
DO - 10.1002/ajh.25318
M3 - Article
C2 - 30328139
AN - SCOPUS:85056663050
SN - 0361-8609
VL - 94
SP - 74
EP - 79
JO - American journal of hematology
JF - American journal of hematology
IS - 1
ER -