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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.

Original publication

DOI

10.1182/blood-2013-11-536557

Type

Journal article

Journal

Blood

Publication Date

03/04/2014

Volume

123

Pages

2157 - 2160

Keywords

DNA Mutational Analysis, Enhancer of Zeste Homolog 2 Protein, Humans, Isocitrate Dehydrogenase, Janus Kinase 1, Janus Kinase 2, Mutation, Nuclear Proteins, Polycomb Repressive Complex 2, Primary Myelofibrosis, Prognosis, Protein Kinase Inhibitors, Pyrazoles, Repressor Proteins, Ribonucleoproteins, Serine-Arginine Splicing Factors, Treatment Outcome