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

Raajit K. Rampal, John O. Mascarenhas, Heidi E. Kosiorek, Leah Price, Dmitriy Berenzon, Elizabeth Hexner, Camille N. Abboud, Marina Kremyanskaya, Rona Singer Weinberg, Mohamed E. Salama, Kamal Menghrajani, Vesna Najfeld, Lonette Sandy, Mark L. Heaney, Ross L. Levine, Ruben A. Mesa, Amylou C. Dueck, Judith D. Goldberg, Ronald Hoffman

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


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 1 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.

Original languageEnglish (US)
Pages (from-to)3572-3580
Number of pages9
JournalBlood Advances
Issue number24
StatePublished - Dec 26 2018

ASJC Scopus subject areas

  • Hematology


Dive into the research topics of 'Safety and efficacy of combined ruxolitinib and decitabine in accelerated and blast-phase myeloproliferative neoplasms'. Together they form a unique fingerprint.

Cite this