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Mutations in histone modulators are associated with prolonged survival during azacitidine therapy.
- Source :
-
Oncotarget [Oncotarget] 2016 Apr 19; Vol. 7 (16), pp. 22103-15. - Publication Year :
- 2016
-
Abstract
- Early therapeutic decision-making is crucial in patients with higher-risk MDS. We evaluated the impact of clinical parameters and mutational profiles in 134 consecutive patients treated with azacitidine using a combined cohort from Karolinska University Hospital (n=89) and from King's College Hospital, London (n=45). While neither clinical parameters nor mutations had a significant impact on response rate, both karyotype and mutational profile were strongly associated with survival from the start of treatment. IPSS high-risk cytogenetics negatively impacted overall survival (median 20 vs 10 months; p<0.001), whereas mutations in histone modulators (ASXL1, EZH2) were associated with prolonged survival (22 vs 12 months, p=0.01). This positive association was present in both cohorts and remained highly significant in the multivariate cox model. Importantly, patients with mutations in histone modulators lacking high-risk cytogenetics showed a survival of 29 months compared to only 10 months in patients with the opposite pattern. While TP53 was negatively associated with survival, neither RUNX1-mutations nor the number of mutations appeared to influence survival in this cohort. We propose a model combining histone modulator mutational screening with cytogenetics in the clinical decision-making process for higher-risk MDS patients eligible for treatment with azacitidine.<br />Competing Interests: CONFLICTS OF INTERESTGhulam Mufti: has received research funding from Celgene and been part of their advisory board.Eva Hellström-Lindberg: has received research grant from Celgene for the national MDS registry.Martin Jädersten: has recieved honoraria for lectures for Celgene.Austin Kulasekararaj: has recieved honoraria for advisory board and lectures for Celgene.
- Subjects :
- Adult
Aged
Aged, 80 and over
Antimetabolites, Antineoplastic therapeutic use
Azacitidine therapeutic use
DNA Mutational Analysis
Female
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Mutation
Myelodysplastic Syndromes drug therapy
Myelodysplastic Syndromes mortality
Prognosis
Proportional Hazards Models
Treatment Outcome
Biomarkers analysis
Histones genetics
Myelodysplastic Syndromes genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 7
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 26959885
- Full Text :
- https://doi.org/10.18632/oncotarget.7899