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, PhD^1,2,3; Valeria Santini, MD^4,5; Sylvain Thepot, MD^3,6; Lionel Ades, MD, PhD^1,3,7; Cendrine Chaffaut, MSc⁸; Aristoteles Giagounidis, MD^9,10; Margot Morabito, BSc¹¹; Nathalie Droin, PhD¹¹; Michael Lübbert, MD^10,12; Rosa Sapena, PhD³; Stanislas Nimubona, MD^3,13; Jean Goasguen, MD¹⁴; Eric Wattel, MD, PhD^3,15; Gina Zini, MD, PhD^16,17; Jose Miguel Torregrosa Diaz, MD^3,18; Ulrich Germing, MD^10,19; Anna Maria Pelizzari, MD^5,20; Sophie Park, MD, PhD^3,21; Nadja Jaekel, MD^10,22; Georgia Metzgeroth, MD^10,23; Francesco Onida, MD^5,24; Robert Navarro, MD^3,25; Andrea Patriarca, MD^5,26; Aspasia Stamatoullas, MD^3,27; Katharina Götze, MD^10,28; Martin Puttrich, MSc^10,29; Sandra Mossuto, MSc⁵; Eric Solary, MD3,^11,30; Silke Gloaguen, MSc^10,31; Sylvie Chevret, MD, PhD⁸; Fatiha Chermat, DMD³; Uwe Platzbecker, MD^10,31; and Pierre Fenaux, MD, PhD^1,3,7

Source: DOI: 10.1200/JCO.22.00437 Journal of Clinical Oncology 41, no. 10 (April 01, 2023) 1888-1897

Dr. Maen Hussein's Thoughts

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

PURPOSE

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).

PATIENTS AND METHODS

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.

RESULTS

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).

CONCLUSION

Compared with HY, frontline treatment with DAC did not improve EFS in patients with advanced myeloproliferative CMML (ClinicalTrials.gov 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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