TY - JOUR
T1 - Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia
T2 - A phase 2 trial
AU - Braun, Thorsten
AU - Itzykson, Raphael
AU - Renneville, Aline
AU - De Renzis, Benoit
AU - Dreyfus, François
AU - Laribi, Kamel
AU - Bouabdallah, Krimo
AU - Vey, Norbert
AU - Toma, Andrea
AU - Recher, Christian
AU - Royer, Bruno
AU - Joly, Bertrand
AU - Vekhoff, Anne
AU - Lafon, Ingrid
AU - Sanhes, Laurence
AU - Meurice, Guillaume
AU - Oréar, Cédric
AU - Preudhomme, Claude
AU - Gardin, Claude
AU - Ades, Lionel
AU - Fontenay, Michaela
AU - Fenaux, Pierre
AU - Droin, Nathalie
AU - Solary, Eric
PY - 2011/10/6
Y1 - 2011/10/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80053648633&partnerID=8YFLogxK
U2 - 10.1182/blood-2011-05-352039
DO - 10.1182/blood-2011-05-352039
M3 - Article
C2 - 21828134
AN - SCOPUS:80053648633
SN - 0006-4971
VL - 118
SP - 3824
EP - 3831
JO - Blood
JF - Blood
IS - 14
ER -