Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial

Blood - Tập 118 - Trang 3824-3831 - 2011
Thorsten Braun1, Raphael Itzykson1,2, Aline Renneville3, Benoit de Renzis4, François Dreyfus5, Kamel Laribi6, Krimo Bouabdallah7, Norbert Vey8, Andrea Toma9, Christian Recher10, Bruno Royer11, Bertrand Joly12, Anne Vekhoff13, Ingrid Lafon14, Laurence Sanhes15, Guillaume Meurice2, Cédric Oréar2, Claude Preudhomme3, Claude Gardin1, Lionel Ades1
1Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris (AP-HP), Hématologie Clinique, University Paris XIII, Bobigny, France;
2Inserm Unité Mixte de Recherche (UMR) 1009, Institut Gustave Roussy; University Paris-Sud XI, Villejuif, France;
3Centre Hospitalier Universitaire (CHU) de Lille, Hématologie biologique, University of Lille, Lille, France;
4CHU Estaing, Hématologie clinique adulte et thérapie cellulaire, Clermont Ferrand, France;
5Hôpital Cochin, AP-HP, Hématologie Clinique, University Paris V, Paris, France;
6Centre Hospitalier (CH) du Mans, Hématologie et Oncologie, Le Mans, France;
7Hôpital Haut-Lévêque, Maladies du Sang, University of Bordeaux, Bordeaux, France;
8Institut Paoli-Calmette, Département d'Hématologie, Marseille, France;
9Hôpital Henri Mondor, AP-HP, Hématologie Clinique, University Paris XII, Créteil, France;
10CHU de Toulouse, Hématologie Clinique, Hôpital Purpan, Inserm UMR 1037, Cancer Research Center of Toulouse, Centre National de la Recherche Scientifique (CNRS) ERL 5294, Université Toulouse III Paul Sabatier, Toulouse, France;
11CHU Amiens, Service d'Hématologie Clinique, University of Amiens, Amiens, France;
12CH Sud Francilien, Hématologie Clinique, Corbeil Essonnes, France;
13Hôpital Saint-Antoine, AP-HP, Hématologie Clinique, University Paris IV, Paris, France;
14CHU Le Bocage, Hématologie Clinique, University of Burgundy, Dijon, France;
15CH de Perpignan, Hématologie Clinique, Perpignan, France; and

Tóm tắt

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.

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Blood

Tập 118

3824-3831

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