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A phase II study of guadecitabine in higher-risk myelodysplastic syndrome and low blast count acute myeloid leukemia after azacitidine failure
- Source :
- Haematologica
- Publication Year :
- 2019
- Publisher :
- Ferrata Storti Foundation, 2019.
-
Abstract
- High-risk myelodysplastic syndrome/acute myeloid leukemia patients have a very poor survival after azacitidine failure. Guadecitabine (SGI-110) is a novel subcutaneous hypomethylating agent which results in extended decitabine exposure. This multicenter phase II study evaluated the efficacy and safety of guadecitabine in high-risk myelodysplastic syndrome and low blast count acute myeloid leukemia patients refractory or relapsing after azacitidine. We included 56 patients with a median age of 75 years [Interquartile Range (IQR) 69-76]. Fifty-five patients received at least one cycle of guadecitabine (60 mg/m2/d subcutaneously days 1-5 per 28-day treatment cycles), with a median of 3 cycles (range, 0-27). Eight (14.3%) patients responded, including two complete responses; median response duration was 11.5 months. Having no or few identified somatic mutations was the only factor predicting response (P=0.035). None of the 11 patients with TP53 mutation responded. Median overall survival was 7.1 months, and 17.9 months in responders (3 of whom had overall survival >2 years). In multivariate analysis, IPSS-R (revised International Prognostic Scoring System) score other than very high (P=0.03) primary versus secondary azacitidine failure (P=0.01) and a high rate of demethylation in blood during the first cycle of treatment (P=0.03) were associated with longer survival. Thus, guadecitabine can be effective, sometimes yielding relatively prolonged survival, in a small proportion of high-risk myelodysplastic syndrome/low blast count acute myeloid leukemia patients who failed azacitidine. (Trial registered at clinicaltrials.gov identifier: 02197676).
- Subjects :
- Male
Risk
medicine.medical_specialty
Azacitidine
Decitabine
Gastroenterology
Article
03 medical and health sciences
0302 clinical medicine
Interquartile range
Internal medicine
medicine
Humans
Survival analysis
Aged
business.industry
Myeloid leukemia
Hematology
medicine.disease
Survival Analysis
Leukemia
Leukemia, Myeloid, Acute
Treatment Outcome
Hypomethylating agent
International Prognostic Scoring System
Myelodysplastic Syndromes
Female
business
030215 immunology
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 15928721 and 03906078
- Volume :
- 104
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Haematologica
- Accession number :
- edsair.doi.dedup.....ee6903c0ff331afeb69606b2465b48cb