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

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/m ² /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 × 10 ⁹ /L and 31.2 × 10 ⁹ /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).
Competing Interests: Raphael ItzyksonHonoraria: AbbVie, Astellas Pharma, Celgene/Bristol Myers Squibb, Novartis, ServierConsulting or Advisory Role: Amgen, Celgene/Bristol Myers Squibb, Daiichi Sankyo Europe GmbH, Novartis, ServierResearch Funding: Janssen (Inst), Novartis (Inst) Valeria SantiniHonoraria: Celgene/Bristol Myers Squibb, NovartisConsulting or Advisory Role: Celgene/Bristol Myers Squibb, Novartis, Menarini, Takeda, Gilead Sciences, AbbVie, Syros Pharmaceuticals, ServierResearch Funding: Celgene (Inst)Travel, Accommodations, Expenses: Janssen-Cilag, Celgene Sylvain ThepotHonoraria: Astellas Pharma, Novartis, AbbVie, BMSiTravel, Accommodations, Expenses: Amgen, AbbVie Lionel AdesHonoraria: Celgene, AbbVie, Jazz Pharmaceuticals, BerGenBio, Silence Therapeutics, NovartisResearch Funding: Celgene (Inst) Aristoteles GiagounidisStock and Other Ownership Interests: Novartis, RocheHonoraria: Amgen, Novartis, Bristol Myers Squibb/CelgeneConsulting or Advisory Role: Bristol Myers Squibb/Celgene Michael LübbertConsulting or Advisory Role: Syros Pharmaceuticals, AbbVieResearch Funding: Johnson & Johnson (Inst) Ulrich GermingHonoraria: Celgene, Novartis, Jazz PharmaceuticalsConsulting or Advisory Role: CelgeneResearch Funding: Celgene (Inst), Novartis (Inst) Anna Maria PelizzariTravel, Accommodations, Expenses: Janssen-Ortho Sophie ParkHonoraria: Novartis/Ipsen, Bristol Myers Squibb/CelgeneConsulting or Advisory Role: Novartis, Pfizer, Bristol Myers Squibb/CelgeneResearch Funding: Pfizer, TakedaTravel, Accommodations, Expenses: Pfizer, Novartis Nadja JaekelHonoraria: Novartis Georgia MetzgerothHonoraria: Roche Pharma AG, Novartis, GlaxoSmithKlineConsulting or Advisory Role: GlaxoSmithKline Francesco OnidaTravel, Accommodations, Expenses: Takeda, Kyowa Kirin International, Medac Andrea PatriarcaConsulting or Advisory Role: Sanofi, SOBISpeakers' Bureau: Novartis Italy, Incyte Aspasia StamatoullasConsulting or Advisory Role: Pfizer, JanssenTravel, Accommodations, Expenses: Pfizer Katharina GötzeHonoraria: BMSConsulting or Advisory Role: BMS, AbbVie, Servier/PfizerResearch Funding: BMS Eric SolaryResearch Funding: Servier (Inst)Travel, Accommodations, Expenses: Novartis Uwe PlatzbeckerHonoraria: Celgene/Jazz, AbbVie, Curis, Geron, JanssenConsulting or Advisory Role: Celgene/Jazz, Novartis, BMS GmbH & Co. KGResearch Funding: Amgen (Inst), Janssen (Inst), Novartis (Inst), BerGenBio (Inst), Celgene (Inst), Chris (Inst)Patents, Royalties, Other Intellectual Property: part of a patent for a TFR-2 antibody (Rauner et al Nature Metabolics 2019)Travel, Accommodations, Expenses: Celgene Pierre FenauxHonoraria: CelgeneResearch Funding: Celgene (Inst)No other potential conflicts of interest were reported.