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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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 |
Journal | American journal of hematology
(Am J Hematol)
Vol. 94
Issue 1
Pg. 74-79
(01 2019)
ISSN: 1096-8652 [Electronic] United States |
PMID | 30328139
(Publication Type: Clinical Trial, Phase II, Journal Article)
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Copyright | © 2018 Wiley Periodicals, Inc. |
Chemical References |
- Antineoplastic Agents
- Homoharringtonine
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Topics |
- Aged
- Aged, 80 and over
- Antineoplastic Agents
(adverse effects, therapeutic use)
- Chromosome Aberrations
- DNA Mutational Analysis
- Disease-Free Survival
- Drug Administration Schedule
- Drug Resistance, Neoplasm
- Drug Substitution
- Fatigue
(chemically induced)
- Febrile Neutropenia
(chemically induced)
- Female
- Gastrointestinal Diseases
(chemically induced)
- Hemorrhage
(chemically induced)
- Homoharringtonine
(adverse effects, therapeutic use)
- Humans
- Kaplan-Meier Estimate
- Leukemia, Myelomonocytic, Chronic
(drug therapy, genetics)
- Male
- Middle Aged
- Myelodysplastic Syndromes
(drug therapy, genetics)
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