Impact of Mutational Status on Outcomes in Myelofibrosis Patients Treated With Ruxolitinib in the COMFORT-II Study

Blood. 2014 Apr 3;123(14):2157-60. doi: 10.1182/blood-2013-11-536557. Epub 2014 Jan 23.


The JAK1/JAK2 inhibitor ruxolitinib produced significant reductions in splenomegaly and symptomatic burden and improved survival in patients with myelofibrosis (MF), irrespective of their JAK2 mutation status, in 2 phase III studies against placebo (COMFORT-I) and best available therapy (COMFORT-II). We performed a comprehensive mutation analysis to evaluate the impact of 14 MF-associated mutations on clinical outcomes in 166 patients included in COMFORT-II. We found that responses in splenomegaly and symptoms, as well as the risk of developing ruxolitinib-associated anemia and thrombocytopenia, occurred at similar frequencies across different mutation profiles. Ruxolitinib improved survival independent of mutation profile and reduced the risk of death in patients harboring a set of prognostically detrimental mutations (ASXL1, EZH2, SRSF2, IDH1/2) with an hazard ratio of 0.57 (95% confidence interval: 0.30-1.08) vs best available therapy. These data indicate that clinical efficacy and survival improvement may occur across different molecular subsets of patients with MF treated with ruxolitinib.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Mutational Analysis
  • Enhancer of Zeste Homolog 2 Protein
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Janus Kinase 1 / genetics
  • Janus Kinase 2 / genetics
  • Mutation
  • Nuclear Proteins / genetics
  • Polycomb Repressive Complex 2 / genetics
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / genetics*
  • Primary Myelofibrosis / mortality
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use*
  • Repressor Proteins / genetics
  • Ribonucleoproteins / genetics
  • Serine-Arginine Splicing Factors
  • Treatment Outcome


  • ASXL1 protein, human
  • INCB018424
  • Nuclear Proteins
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Repressor Proteins
  • Ribonucleoproteins
  • SRSF2 protein, human
  • Serine-Arginine Splicing Factors
  • Isocitrate Dehydrogenase
  • isocitrate dehydrogenase 2, human
  • IDH1 protein, human
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2
  • JAK2 protein, human
  • Janus Kinase 1
  • Janus Kinase 2