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Efficacy of azacitidine is independent of molecular and clinical characteristics - an analysis of 128 patients with myelodysplastic syndromes or acute myeloid leukemia and a review of the literature
- Source :
- Oncotarget
- Publication Year :
- 2018
- Publisher :
- Impact Journals, LLC, 2018.
-
Abstract
- Azacitidine is the first drug to demonstrate a survival benefit for patients with MDS. However, only half of patients respond and almost all patients eventually relapse. Limited and conflicting data are available on predictive factors influencing response. We analyzed 128 patients from two institutions with MDS or AML treated with azacitidine to identify prognostic indicators. Genetic mutations in ASXL1, RUNX1, DNMT3A, IDH1, IDH2, TET2, TP53, NRAS, KRAS, FLT3, KMT2A-PTD, EZH2, SF3B1, and SRSF2 were assessed by next-generation sequencing. With a median follow up of 5.6 years median survival was 1.3 years with a response rate of 49%. The only variable with significant influence on response was del(20q). All 6 patients responded (p = 0.012) but survival was not improved. No other clinical, cytogenetic or molecular marker for response or survival was identified. Interestingly, patients from poor-risk groups as high-risk cytogenetics (55%), t-MDS/AML (54%), TP53 mutated (48%) or relapsed after chemotherapy (60%) showed a high response rate. Factors associated with shorter survival were low platelets, AML vs. MDS, therapy-related disease, TP53 and KMT2A-PTD. In multivariate analysis anemia, platelets, FLT3-ITD, and therapy-related disease remained in the model. Poor-risk factors such as del(7q)/-7, complex karyotype, ASXL1, RUNX1, EZH2, and TP53 did not show an independent impact. Thus, no clear biomarker for response and survival can be identified. Although a number of publications on predictive markers for response to AZA exist, results are inconsistent and improved response rates did not translate to improved survival. Here, we provide a comprehensive overview comparing the studies published to date.
- Subjects :
- 0301 basic medicine
Neuroblastoma RAS viral oncogene homolog
Oncology
Clinical Review
azacitidine
medicine.medical_specialty
Azacitidine
medicine.disease_cause
03 medical and health sciences
0302 clinical medicine
Median follow-up
hemic and lymphatic diseases
Internal medicine
medicine
Response rate (survey)
hypomethylating agents
business.industry
Myelodysplastic syndromes
Myeloid leukemia
targeted therapy
medicine.disease
myelodysplastic syndromes
030104 developmental biology
030220 oncology & carcinogenesis
Biomarker (medicine)
response prediction
KRAS
business
medicine.drug
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....2a11496acad02ba0632c2dc7a35155b8