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Blood Adv. 2018 Dec 26;2(24):3572-3580. doi: 10.1182/bloodadvances.2018019661.

Safety and efficacy of combined ruxolitinib and decitabine in accelerated and blast-phase myeloproliferative neoplasms.

Author information

Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
Mayo Clinic Scottsdale, Scottsdale, AZ.
Division of Biostatistics, New York University School of Medicine, New York, NY.
Wake Forest Baptist Health, Winston-Salem, NC.
Division of Hematology Oncology, Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, PA.
Division of Oncology, Washington University School of Medicine, St. Louis, MO.
New York Blood Center, New York, NY.
Department of Pathology, Mayo Clinic Cancer Center, Rochester, MN.
Department of Medicine, Columbia University Medical Center, New York, NY.
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY; and.
Mays Cancer Center, University of Texas at San Antonio, San Antonio, TX.


Myeloproliferative neoplasms (MPN), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to evolve into accelerated and blast-phase disease (MPN-AP/BP), carrying a dismal prognosis. Conventional antileukemia therapy has limited efficacy in this setting. Thus, MPN-AP/BP is an urgent unmet clinical need. Modest responses to hypomethylating agents and single-agent ruxolitinib have been reported. More recently, combination of ruxolitinib and decitabine has demonstrated synergistic in vitro activity in human and murine systems. These observations led us to conduct a phase 1 study to explore the safety of combined decitabine and dose-escalated ruxolitinib in patients with MPN-AP/BP. A total of 21 patients were accrued to this multicenter study. Ruxolitinib was administered at doses of 10, 15, 25, or 50 mg twice daily in combination with decitabine (20 mg/m2 per day for 5 days) in 28-day cycles. The maximum tolerated dose was not reached. The most common reasons for study discontinuation were toxicity/adverse events (37%) and disease progression (21%). Fourteen patients died during study treatment period or follow-up. The median overall survival for patients on study was 7.9 months (95% confidence interval, 4.1-not reached). Among evaluable patients, the overall response rate by protocol-defined criteria (complete remission with incomplete count recovery + partial remission) was 9/17 (53%) and by intention-to-treat analysis was 9/21 (42.9%). The combination of decitabine and ruxolitinib was generally well tolerated by patients with MPN-AP/BP and demonstrates potentially promising clinical activity. A phase 2 trial evaluating the efficacy of this combination regimen is ongoing within the Myeloproliferative Disorder Research Consortium.

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