TY - JOUR
T1 - Impact of mutational status on outcomes in myelofibrosis patients treated with ruxolitinib in the COMFORT-II study
AU - Guglielmelli, Paola
AU - Biamonte, Flavia
AU - Rotunno, Giada
AU - Artusi, Valentina
AU - Artuso, Lucia
AU - Bernardis, Isabella
AU - Tenedini, Elena
AU - Pieri, Lisa
AU - Paoli, Chiara
AU - Mannarelli, Carmela
AU - Fjerza, Rajmonda
AU - Rumi, Elisa
AU - Stalbovskaya, Viktoriya
AU - Squires, Matthew
AU - Cazzola, Mario
AU - Manfredini, Rossella
AU - Harrison, Claire
AU - Tagliafico, Enrico
AU - Vannucchi, Alessandro M
AU - COMFORT-II Investigators
AU - Kluin-Nelemans, H.C.
PY - 2014/4/3
Y1 - 2014/4/3
N2 - 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.
AB - 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.
KW - DNA Mutational Analysis
KW - Humans
KW - Isocitrate Dehydrogenase
KW - Janus Kinase 1
KW - Janus Kinase 2
KW - Mutation
KW - Nuclear Proteins
KW - Polycomb Repressive Complex 2
KW - Primary Myelofibrosis
KW - Prognosis
KW - Protein Kinase Inhibitors
KW - Pyrazoles
KW - Repressor Proteins
KW - Ribonucleoproteins
KW - Treatment Outcome
U2 - 10.1182/blood-2013-11-536557
DO - 10.1182/blood-2013-11-536557
M3 - Article
C2 - 24458439
SN - 0006-4971
VL - 123
SP - 2157
EP - 2160
JO - Blood
JF - Blood
IS - 14
ER -