title: Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial.
abstract: Hydroxyurea is the standard therapy of chronic myelomonocytic leukemia (CMML) presenting with advanced myeloproliferative and/or myelodysplastic features. Response to hypomethylating agents has been reported in heterogeneous series of CMML. We conducted a phase 2 trial of decitabine (DAC) in 39 patients with advanced CMML defined according to a previous trial. Median number of DAC cycles was 10 (range, 1-24). Overall response rate was 38% with 4 complete responses (10%), 8 marrow responses (21%), and 3 stable diseases with hematologic improvement (8%). Eighteen patients (46%) demonstrated stable disease without hematologic improvement, and 6 (15%) progressed to acute leukemia. With a median follow-up of 23 months, overall survival was 48% at 2 years. Mutations in ASXL1, TET2, AML1, NRAS, KRAS, CBL, FLT3, and janus kinase 2 (JAK2) genes, and hypermethylation of the promoter of the tumor suppressor gene TIF1γ, did not predict response or survival on DAC therapy. Lower CJUN and CMYB gene expression levels independently predicted improved overall survival. This trial confirmed DAC efficacy in approximately 40% of CMML patients with advanced myeloproliferative or myelodysplastic features and suggested that CJUN and CMYB expression could be potential biomarkers in this setting. This trial is registered at EudraCT (eudract.ema.europa.eu) as #2008-000470-21 and www.clinicaltrials.gov as #NCT01098084.
authors.affiliation: Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris (AP-HP), Hématologie Clinique, University Paris XIII, Bobigny, France.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Braun
authors.forename: Raphael
authors.initials: R
authors.lastname: Itzykson
authors.forename: Aline
authors.initials: A
authors.lastname: Renneville
authors.forename: Benoit
authors.initials: B
authors.lastname: de Renzis
authors.forename: François
authors.initials: F
authors.lastname: Dreyfus
authors.forename: Kamel
authors.initials: K
authors.lastname: Laribi
authors.forename: Krimo
authors.initials: K
authors.lastname: Bouabdallah
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.forename: Andrea
authors.initials: A
authors.lastname: Toma
authors.forename: Christian
authors.initials: C
authors.lastname: Recher
authors.forename: Bruno
authors.initials: B
authors.lastname: Royer
authors.forename: Bertrand
authors.initials: B
authors.lastname: Joly
authors.forename: Anne
authors.initials: A
authors.lastname: Vekhoff
authors.forename: Ingrid
authors.initials: I
authors.lastname: Lafon
authors.forename: Laurence
authors.initials: L
authors.lastname: Sanhes
authors.forename: Guillaume
authors.initials: G
authors.lastname: Meurice
authors.forename: Cédric
authors.initials: C
authors.lastname: Oréar
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
authors.forename: Claude
authors.initials: C
authors.lastname: Gardin
authors.forename: Lionel
authors.initials: L
authors.lastname: Ades
authors.forename: Michaela
authors.initials: M
authors.lastname: Fontenay
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Nathalie
authors.initials: N
authors.lastname: Droin
authors.forename: Eric
authors.initials: E
authors.lastname: Solary
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077209:Decitabine; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine