title: The effect of long-term ruxolitinib treatment on JAK2p.V617F allele burden in patients with myelofibrosis.
abstract: The JAK2 c.1849G>T (p.V617F) mutation leads to constitutive activation of Janus kinase (JAK)2 and contributes to dysregulated JAK signaling in myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). In the phase 3 Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment-I trial, patients with MF, post-PV MF, or post-ET MF achieved significant reductions in splenomegaly and improvements in symptoms with ruxolitinib vs placebo at week 24. This long-term follow-up analysis was performed to determine whether ruxolitinib therapy altered the JAK2p.V617F allele burden in JAK2p.V617F-positive patients. Assessments at baseline and weeks 24, 48, 120, 144, 168, and 216 demonstrated reductions in allele burden from baseline with ruxolitinib treatment that correlated with spleen volume reductions. Of 236 JAK2p.V617F-positive patients analyzed, 20 achieved partial and 6 achieved complete molecular responses, with median times to response of 22.2 and 27.5 months, respectively. Allele burden reductions were greater in patients with shorter disease duration, which suggests a potential benefit of earlier treatment. This trial was registered at www.clinicaltrials.gov as #NCT00952289.
authors.affiliation: University of Utah Huntsman Cancer Institute, Salt Lake City, UT;
authors.forename: Michael
authors.initials: M
authors.lastname: Deininger
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA;
authors.forename: Jerald
authors.initials: J
authors.lastname: Radich
authors.affiliation: Incyte Corporation, Wilmington, DE; and.
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Burn
authors.affiliation: Incyte Corporation, Wilmington, DE; and.
authors.forename: Reid
authors.initials: R
authors.lastname: Huber
authors.affiliation: Incyte Corporation, Wilmington, DE; and.
authors.forename: Dilan
authors.initials: D
authors.lastname: Paranagama
authors.affiliation: The University of Texas, MD Anderson Cancer Center, Houston, TX.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000483:Alleles; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D008297:Male; D009570:Nitriles; D017354:Point Mutation; D055728:Primary Myelofibrosis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D013154:Spleen / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013163:Splenomegaly / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology
chemical_list: D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; C507924:JAK2 protein, human; D053614:Janus Kinase 2