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Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN

Elias Jabbour, Nicholas J. Short, Guillermo Montalban-Bravo, Xuelin Huang, Carlos Bueso-Ramos, Wei Qiao, Hui Yang, Chong Zhao, Tapan Kadia, Gautam Borthakur, Naveen Pemmaraju, Koji Sasaki, Zeev Estrov, Jorge Cortes, Farhad Ravandi, Yesid Alvarado, Rami Komrokji, Mikkael A. Sekeres, David P. Steensma, Amy DeZern, Gail Roboz, Hagop Kantarjian and Guillermo Garcia-Manero

Data supplements

Article Figures & Data

Figures

  • Figure 1.

    Mutation landscape of enrolled patients. (A) Frequency of detected mutations based on World Health Organization 2016 subtype. MDS-EB, MDS with excess blasts; MDS-MLD, MDS with multilineage dysplasia; MDS/MPN-U, MDS/MPN unclassifiable; MDS-SLD, MDS with single lineage dysplasia. Frequencies are expressed for total number of patients studied for each particular mutation. (B-C) Circos plot and table describing frequencies of identified mutations based on treatment group.

  • Figure 2.

    Subgroup analysis: a forest plot showing the odds ratios for overall response of various subgroups by treatment group.

  • Figure 3.

    Kaplan-Meier curves for EFS. By treatment group (A) and survival by treatment arm (B).

Tables

  • Table 1.

    Patient characteristics

    Parameter n (%)/median [range]Overall (n = 113)Decitabine (N = 73)Azacitidine (N = 40)
    Age, years70 [44-88]70 [44-88]70 [53-84]
    WHO diagnosis
     RCUD15 (13)10 (14)5 (13)
     RCMD40 (35)29 (40)11 (28)
     MDS with ringed sideroblasts3 (3)2 (3)1 (3)
     MDS-EB25 (22)14 (19)11 (28)
     5q-2 (2)02 (5)
     MDS-U6 (5)6 (8)0
     MDS/MPN-U6 (5)2 (3)4 (10)
     CMML16 (14)10 (14)6 (15)
    Therapy-related MDS20 (18)13 (18)7 (18)
    ≥2 cytopenias68 (50)34 (47)22 (55)
    Transfusion dependence59 (52)39 (53)20 (50)
    BM blasts percentage3 [0-10]2 [0-10]3 [0-10]
    Blasts ≥5%32 (28)21 (29)11 (27)
    Cytogenetic risk (IPSS)
     Good69 (61)43 (63)26 (65)
     Intermediate30 (27)17 (23)13 (33)
     Poor11 (10)10 (14)1 (3)
    IPSS risk group
     Low22 (19)16 (22)6 (15)
     Intermediate-191 (81)57 (78)34 (85)
    IPSS-R risk group
     Very low14 (12)10 (14)4 (10)
     Low41 (36)25 (34)16 (40)
     Intermediate34 (30)21 (29)13 (33)
     High23 (20)16 (22)7 (18)
     Very high1 (1)1 (1)0
    MDACC LR-MDS score
     Low13 (11)10 (14)3 (8)
     Intermediate52 (46)35 (48)14 (43)
     High48 (42)28 (38)20 (40)
    Prior therapy
     Growth factors22 (19)12 (16)10 (25)
     Others9 (8)5 (7)4 (10)
    Time from diagnosis, weeks5 [1-271]6 [1-216]4 [1-271]
    • BM, bone marrow; MDACC, MD Anderson Cancer Center; MDS-EB, MDS with excess blasts; MDS-U, MDS, unclassified; MPN-U, myeloproliferative neoplasm, unclassified; RCMD, refractory cytopenia with multilineage dysplasia; RCUD, refractory cytopenia with unilineage dysplasia; WHO, World Health Organization.

  • Table 2.

    Response

    ParameterOverall, n (%)Decitabine, n (%)Azacitidine, n (%)P
    Morphologic response, N1097039
     CR40 (37)26 (37)14 (36)
     mCR8 (7)6 (9)2 (5)
     HI20 (18)17 (24)3 (8)
     Overall68 (62)49 (70)19 (49).03
    Transfusion response, N573819
     RBC11/46 (24)8/29 (28)3/17 (18)
     Platelets3/5 (60)3/4 (75)0/1
     RBC + Platelets1/6 (17)1/5 (20)0/1
     Overall15 (26)12 (32)3 (16).2
    Cytogenetic response, N442816
     Complete8 (18)7 (25)1 (6)
     Partial13 (30)10 (36)3 (19)
     Overall21 (48)17 (61)4 (25).02
    Morphologic response (BM blasts ≥5%), N322111
     CR14 (44)12 (57)2 (18)
     mCR8 (25)6 (29)2 (18)
     HI3 (9)3 (14)0
     Overall25 (78)21 (100)4 (36)<.001
    Hematologic response (BM blasts <5%), N724527
     ≥1 lineage29 (40)16 (36)13 (48)
     All lineages17 (24)10 (22)7 (26)
    • HI, hematologic improvement; RBC, red blood cell.

  • Table 3.

    Univariate and multivariate analysis for OS (overall population)

    VariableUnivariate analysisMultivariate analysis
    HR95% CIPHR95% CIP
    Age1.9480.590-6.438.274
     ≤60 y
     >60 y
    WHO diagnosis1.3430.594-3.034.478
     MDS
     MDS/MPN
    Cytopenias2.2301.015-4.899.0464.1970.340-51.865.264
     0-1
     ≥2
    BM blasts1.3930.657-2.957.387
     <5%
     ≥5
    Cytogenetic risk0.5000.213-1.170.110
     Good
     Others
    Transfusion2.3041.070-4.959.0331.2420.186-8.301.823
     Dependent
     Independent
    IPSS risk1.1440.398-3.293.803
     Low
     Intermediate 1
    IPSS-R risk1.2630.519-3.188.406
     High or very high
     Others
    MDA LR-MDS score1.2580.607-2.606.537
     High (category 3)
     Others
    Response0.3780.161-0.890.0260.0450.002-0.995.047
     CR
     Non-CR
    DNMT3A5.7191.621-20.181.00725.9300.904-743.842.057
     Wild-type
     Mutated
    TP533.6821.228-11.035.020136.7645.292-3534.38.003
     Wild-type
     Mutated
    ZRSR245.4752.843-727.310.00794.8652.528-3559.721.014
     Wild-type
     Mutated
  • Table 4.

    Nonhematologic adverse events observed in at least 3% of patients

    ParameterN (%)
    Decitabine (n = 73)Azacitidine (n = 40)
    All GradesGrade 3All GradesGrade 3
    Nausea11 (15)06 (15)0
    Fatigue6 (8)04 (10)0
    Infection/Neutropenic fever5 (7)4 (5)2 (5)0
    Constipation3 (4)06 (15)0
    Diarrhea2 (3)03 (8)0