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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| Authors: | Nicholas J. Short Elias Jabbour Kiran Naqvi Ami Patel Jing Ning Koji Sasaki Graciela M. Nogueras-Gonzalez Prithviraj Bose Steven M. Kornblau Koichi Takahashi Michael Andreeff Gabriela Sanchez-Petitto Zeev Estrov Courtney D. Dinardo Guillermo Montalban-Bravo Marina Konopleva Yesid Alvarado Kapil N. Bhalla Warren Fiskus Maria Khouri Rubiul Islam Hagop Kantarjian Guillermo Garcia-Manero |
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| Affiliation: | 1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas;2. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas;3. Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas |
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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. |
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