Adding hydroxyurea in combination with ruxolitinib improves clinical responses in hyperproliferative forms of myelofibrosis

Cancer Med. 2019 Jun;8(6):2802-2809. doi: 10.1002/cam4.2147. Epub 2019 Apr 17.


Ruxolitinib, an orally bioavailable and selective inhibitor of Janus kinase 1 (JAK1) and JAK2, significantly reduces splenomegaly and disease-related symptoms in patients with myelofibrosis (MF). However, no clear survival benefit has been demonstrated, which may in part reflect suboptimal drug exposure related to lower dosages needed to minimize hematological toxicity, specifically cytopenias. Furthermore, the optimal management of specific conditions such as leukocytosis or thrombocytosis in patients under ruxolitinib therapy is still undefined. In these cases, combining ruxolitinib with a cytoreductive agent like hydroxyurea might improve hematological response. This observational multi-center study enrolled 20 adult patients with intermediate- or high-risk primary MF, post- polycythemia vera MF, or postessential thrombocythemia MF with hyperproliferative manifestations of the disease and WBC and/or platelet counts not controlled by ruxolitinib therapy. The patients received treatment with a combination of ruxolitinib and hydroxyurea. A clinical response of any type was obtained in 8 patients (40%) during ruxolitinib monotherapy and in 17 patients (85%) during ruxolitinib-hydroxyurea combination (P = 0.003). After a median duration of 12.4 months of combination therapy, 16/20 patients had a hematological response; 14/17 patients who had started combination therapy to control WBC count and 2/3 who started in order to reduce platelets count. The number of patients requiring ruxolitinib dosage reduction or discontinuations was lower during combination therapy and, at the end of follow-up the median ruxolitinib dose was increased in 50% of patients. In conclusion, the combination of hydroxyurea with ruxolitinib yielded a high clinical response rate and increased ruxolitinib exposure in patients with hyperproliferative forms of MF.

Keywords: Janus kinase (JAK) inhibitors; hydroxyurea; primary myelofibrosis; ruxolitinib.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Biomarkers
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hydroxyurea / administration & dosage
  • Hydroxyurea / adverse effects
  • Hydroxyurea / therapeutic use*
  • Janus Kinase Inhibitors / administration & dosage
  • Janus Kinase Inhibitors / adverse effects
  • Janus Kinase Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Nitriles
  • Primary Myelofibrosis / diagnosis*
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / metabolism
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyrimidines
  • Retrospective Studies


  • Antineoplastic Agents
  • Biomarkers
  • Janus Kinase Inhibitors
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • Hydroxyurea