Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia: Results of a Randomized Phase III Trial Within the EMSCO Network

Author(s): Raphael Itzykson, MD, PhD1,2,3; Valeria Santini, MD4,5; Sylvain Thepot, MD3,6; Lionel Ades, MD, PhD1,3,7; Cendrine Chaffaut, MSc8; Aristoteles Giagounidis, MD9,10; Margot Morabito, BSc11; Nathalie Droin, PhD11; Michael Lübbert, MD10,12; Rosa Sapena, PhD3; Stanislas Nimubona, MD3,13; Jean Goasguen, MD14; Eric Wattel, MD, PhD3,15; Gina Zini, MD, PhD16,17; Jose Miguel Torregrosa Diaz, MD3,18; Ulrich Germing, MD10,19; Anna Maria Pelizzari, MD5,20; Sophie Park, MD, PhD3,21; Nadja Jaekel, MD10,22; Georgia Metzgeroth, MD10,23; Francesco Onida, MD5,24; Robert Navarro, MD3,25; Andrea Patriarca, MD5,26; Aspasia Stamatoullas, MD3,27; Katharina Götze, MD10,28; Martin Puttrich, MSc10,29; Sandra Mossuto, MSc5; Eric Solary, MD3,11,30; Silke Gloaguen, MSc10,31; Sylvie Chevret, MD, PhD8; Fatiha Chermat, DMD3; Uwe Platzbecker, MD10,31; and Pierre Fenaux, MD, PhD1,3,7
Source: DOI: 10.1200/JCO.22.00437 Journal of Clinical Oncology 41, no. 10 (April 01, 2023) 1888-1897
Maem Hussein MD

Dr. Maen Hussein's Thoughts

While use of Hydroxyurea for CMML may not be common practice, it is an option.


Hydroxyurea (HY) is a reference treatment of advanced myeloproliferative neoplasms. We conducted a randomized phase III trial comparing decitabine (DAC) and HY in advanced myeloproliferative chronic myelomonocytic leukemias (CMML).


Newly diagnosed myeloproliferative CMML patients with advanced disease were randomly assigned 1:1 to intravenous DAC (20 mg/m2/d days 1-5) or HY (1-4 g/d) in 28-day cycles. The primary end point was event-free survival (EFS), events being death and acute myelomonocytic leukemia (AML) transformation or progression.


One-hundred seventy patients received DAC (n = 84) or HY (n = 86). Median age was 72 and 74 years, and median WBC count 32.5 × 109/L and 31.2 × 109/L in the DAC and HY arms, respectively. Thirty-three percent of DAC and 31% of HY patients had CMML-2. Patients received a median of five DAC and six HY cycles. With a median follow-up of 17.5 months, median EFS was 12.1 months in the DAC arm and 10.3 months in the HY arm (hazard ratio [HR], 0.83; 95% CI, 0.59 to 1.16; P = .27). There was no significant interaction between treatment effect and blast or platelet count, anemia, CMML Prognostic Scoring System, Groupe Francophone des Myelodysplasies, or CMML Prognostic Scoring System–mol risk. Fifty-three (63%) DAC patients achieved a response compared with 30 (35%) HY patients (P = .0004). Median duration of response was similar in both arms (DAC, 16.3 months; HY, 17.4 months; P = .90). Median overall survival was 18.4 months in the DAC arm and 21.9 months in the HY arm (P = .67). Compared with HY, DAC significantly reduced the risk of CMML progression or transformation to acute myelomonocytic leukemia (cause-specific HR, 0.62; 95% CI, 0.41 to 0.94; P = .005) at the expense of death without progression or transformation (cause-specific HR, 1.55; 95% CI, 0.82 to 2.9; P = .04).


Compared with HY, frontline treatment with DAC did not improve EFS in patients with advanced myeloproliferative CMML ( identifier: NCT02214407).

Author Affiliations

1Service Hématologie Adultes, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France2Université de Paris, Génomes, biologie cellulaire et thérapeutique U944, INSERM, CNRS, Paris, France3Groupe Francophone des Myélodysplasies, Paris, France4MDS Unit, DMSC;AOU Careggi, University of Florence, Florence, Italy5Fondazione Italiana Sindromi Mielodisplastiche (FISiM-ets), Bologna, Italy6Hematology Department CHU Angers, Université Angers, Angers, France7Service Hématologie Seniors, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France8SBIM, APHP, Hôpital Saint-Louis, INSERM, UMR-1153, ECSTRA Team, Paris, France9Marien Hospital, Klinik für Hämatologie, Onkologie und klinische Immunologie, D-Düsseldorf, Germany10Deutsche MDS-Studiengruppe, D-04103 Leipzig, Germany11Université Paris Saclay, INSERM U1287, Gustave Roussy Cancer Center, Villejuif, France12Department of Hematology, Oncology and Stem Cell Transplantation, Faculty of Medicine—University Medical Center Freiburg, Freiburg, Germany13Service Hématologie Clinique adulte, CHU de Rennes, Rennes, France14Université de Rennes, Rennes, France15Centre Hospitalier Lyon Sud, Pierre Bénite, France16Hematology, Università Cattolica del S. Cuore, Rome, Italy17Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy18Service d’Hématologie Oncologique et Thérapie Cellulaire, CIC INSERM 1402, University Hospital of Poitiers, Poitiers, France19Heinrich-Heine University Düsseldorf, Universitätsklinik Düsseldorf, Klinik für Hämatologie, Onkologie und Klinische Immunologie, Düsseldorf, Germany20Hematology Unit, ASST Spedali Civili, Brescia, Italy21Université Grenoble Alpes, Hematology Department, CHU Grenoble Alpes, Grenoble, France22University Hospital Halle, Halle, Germany23Department of Hematology and Oncology, University Hospital Mannheim, Heidelberg University, Mannheim, Germany24Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico – University of Milan, Hematology-BMT Unit, Milan, Italy25Service d’Hématologie, CHU Montpellier, Montpellier, France26Hematology Unit, AOU «Maggiore della Carità» and University of Eastern Piedmont, I-28100, Novara, Italy27Centre Henri Becquerel, Rouen, France28Technical University of Munich, Department of Medicine III, Munich, Germany29GWT-TUD GmbH, Dresden, Germany30Department of Hematology, Gustave Roussy Cancer Center, Villejuif, France31Clinic and Polyclinic for Hematology, Cellular Therapy and Hemostaseology, University Hospital Leipzig, Leipzig, Germany

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