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Title: Pioglitazone together with imatinib in chronic myeloid leukemia: A proof of concept study
Authors: Philippe Rousselot
Stéphane Prost
Joelle Guilhot
Lydia Roy
Gabriel Etienne
Laurence Legros
Aude Charbonnier
Valérie Coiteux
Pascale Cony-Makhoul
Francoise Huguet
Emilie Cayssials
Jean Michel Cayuela
Francis Relouzat
Marc Delord
Heriberto Bruzzoni-Giovanelli
Laure Morisset
François Xavier Mahon
François Guilhot
Philippe Leboulch
Universite de Versailles Saint-Quentin-en-Yvelines
CEA Fontenay aux Roses
Centre Hospitalier Universitaire de Poitiers
Hôpital Henri Mondor
Institut Bergonie
Centre Hospitalier Universitaire de Nice
Institut Paoli-Calmettes
Centre Hospitalier Regional Universitaire de Lille
Centre Hospitalier Annecy Genevois
Institut Universitaire du Cancer
Hôpital Saint-Louis
Universite Paris 7- Denis Diderot
CHV Centre Hospitalier de Versailles
Hopital Haut-Lévêque C.H.U de Bordeaux
Brigham and Women's Hospital and Harvard Medical School
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 15-May-2017
Citation: Cancer. Vol.123, No.10 (2017), 1791-1799
Abstract: © 2016 Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. BACKGROUND: We recently reported that peroxisome proliferator-activated receptor γ agonists target chronic myeloid leukemia (CML) quiescent stem cells in vitro by decreasing transcription of STAT5. Here in the ACTIM phase 2 clinical trial, we asked whether pioglitazone add-on therapy to imatinib would impact CML residual disease, as assessed by BCR-ABL1 transcript quantification. METHODS: CML patients were eligible if treated with imatinib for at least 2 years at a stable daily dose, having yielded major molecular response (MMR) but not having achieved molecular response 4.5 (MR4.5) defined by BCR-ABL1/ABL1IS RNA levels ≤ 0.0032%. After inclusion, patients started pioglitazone at a dosage of 30 to 45 mg/day in addition to imatinib. The primary objective was to evaluate the cumulative incidence of patients having progressed from MMR to MR4.5 over 12 months. RESULTS: Twenty-four patients were included (age range, 24-79 years). No pharmacological interaction was observed between the drugs. The main adverse events were weight gain in 12 patients and a mean decrease of 0.4 g/dL in hemoglobin concentration. The cumulative incidence of MR4.5 was 56% (95% confidence interval, 37%-76%) by 12 months, despite a wide range of therapy duration (1.9-15.5 months), and 88% of 17 evaluable patients who were still on imatinib reached MR4.5 by 48 months. The cumulative incidence of MMR to MR4.5 spontaneous conversions over 12 months was estimated to be 23% with imatinib alone in a parallel cohort of patients. CONCLUSION: Pioglitazone in combination with imatinib was well tolerated and yielded a favorable 56% rate. These results provide a proof of concept needing confirmation within a randomized clinical trial (EudraCT 2009-011675-79). Cancer 2017;123:1791–1799. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
ISSN: 10970142
Appears in Collections:Scopus 2016-2017

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