Prognostic role of gene mutations in chronic myelomonocytic leukemia patients treated with hypomethylating agents Journal Article

Authors: Duchmann, M.; Yalniz, F. F.; Sanna, A.; Sallman, D.; Coombs, C. C.; Renneville, A.; Kosmider, O.; Braun, T.; Platzbecker, U.; Willems, L.; Adès, L.; Fontenay, M.; Rampal, R.; Padron, E.; Droin, N.; Preudhomme, C.; Santini, V.; Patnaik, M. M.; Fenaux, P.; Solary, E.; Itzykson, R.
Article Title: Prognostic role of gene mutations in chronic myelomonocytic leukemia patients treated with hypomethylating agents
Abstract: Somatic mutations contribute to the heterogeneous prognosis of chronic myelomonocytic leukemia (CMML). Hypomethylating agents (HMAs) are active in CMML, but analyses of small series failed to identify mutations predicting response or survival. We analyzed a retrospective multi-center cohort of 174 CMML patients treated with a median of 7 cycles of azacitidine (n = 68) or decitabine (n = 106). Sequencing data before treatment initiation were available for all patients, from Sanger (n = 68) or next generation (n = 106) sequencing. Overall response rate (ORR) was 52%, including complete response (CR) in 28 patients (17%). In multivariate analysis, ASXL1 mutations predicted a lower ORR (Odds Ratio [OR] = 0.85, p = 0.037), whereas TET2mut/ASXL1wt genotype predicted a higher CR rate (OR = 1.18, p = 0.011) independently of clinical parameters. With a median follow-up of 36.7 months, overall survival (OS) was 23.0 months. In multivariate analysis, RUNX1mut (Hazard Ratio [HR] = 2.00, p =.011), CBLmut (HR = 1.90, p = 0.03) genotypes and higher WBC (log10(WBC) HR = 2.30, p =.005) independently predicted worse OS while the TET2mut/ASXL1wt predicted better OS (HR = 0.60, p = 0.05). CMML-specific scores CPSS and GFM had limited predictive power. Our results stress the need for robust biomarkers of HMA activity in CMML and for novel treatment strategies in patients with myeloproliferative features and RUNX1 mutations. © 2018 The Authors
Keywords: chronic myelomonocytic leukemia; somatic mutations; prognosis; hypomethylating agents
Journal Title: EBioMedicine
Volume: 31
ISSN: 2352-3964
Publisher: Elsevier Inc.  
Date Published: 2018-05-01
Start Page: 174
End Page: 181
Language: English
DOI: 10.1016/j.ebiom.2018.04.018
PROVIDER: scopus
PUBMED: 29728305
Notes: Article -- Export Date: 1 June 2018 -- Source: Scopus
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MSK Authors
  1. Raajit Kumar Rampal
    146 Rampal
  2. Catherine C Coombs
    15 Coombs