TY - JOUR
T1 - Decitabine Versus Hydroxyurea for Advanced Proliferative Chronic Myelomonocytic Leukemia
T2 - Results of a Randomized Phase III Trial Within the EMSCO Network
AU - Itzykson, Raphael
AU - Santini, Valeria
AU - Thepot, Sylvain
AU - Ades, Lionel
AU - Chaffaut, Cendrine
AU - Giagounidis, Aristoteles
AU - Morabito, Margot
AU - Droin, Nathalie
AU - Lübbert, Michael
AU - Sapena, Rosa
AU - Nimubona, Stanislas
AU - Goasguen, Jean
AU - Wattel, Eric
AU - Zini, Gina
AU - Torregrosa Diaz, Jose Miguel
AU - Germing, Ulrich
AU - Pelizzari, Anna Maria
AU - Park, Sophie
AU - Jaekel, Nadja
AU - Metzgeroth, Georgia
AU - Onida, Francesco
AU - Navarro, Robert
AU - Patriarca, Andrea
AU - Stamatoullas, Aspasia
AU - Götze, Katharina
AU - Puttrich, Martin
AU - Mossuto, Sandra
AU - Solary, Eric
AU - Gloaguen, Silke
AU - Chevret, Sylvie
AU - Chermat, Fatiha
AU - Platzbecker, Uwe
AU - Fenaux, Pierre
N1 - Publisher Copyright:
© 2023 American Society of Clinical Oncology.
PY - 2023/4/1
Y1 - 2023/4/1
N2 - PURPOSEHydroxyurea (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 METHODSNewly 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.RESULTSOne-hundred seventy patients received DAC (n = 84) or HY (n = 86). Median age was 72 and 74 years, and median WBC count 32.5 Ã - 109/L and 31.2 Ã - 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 Systemâ € "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).CONCLUSIONCompared with HY, frontline treatment with DAC did not improve EFS in patients with advanced myeloproliferative CMML (ClinicalTrials.gov identifier: NCT02214407).
AB - PURPOSEHydroxyurea (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 METHODSNewly 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.RESULTSOne-hundred seventy patients received DAC (n = 84) or HY (n = 86). Median age was 72 and 74 years, and median WBC count 32.5 Ã - 109/L and 31.2 Ã - 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 Systemâ € "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).CONCLUSIONCompared with HY, frontline treatment with DAC did not improve EFS in patients with advanced myeloproliferative CMML (ClinicalTrials.gov identifier: NCT02214407).
UR - http://www.scopus.com/inward/record.url?scp=85148211188&partnerID=8YFLogxK
U2 - 10.1200/JCO.22.00437
DO - 10.1200/JCO.22.00437
M3 - Article
C2 - 36455187
AN - SCOPUS:85148211188
SN - 0732-183X
VL - 41
SP - 1888
EP - 1897
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 10
ER -