title: The efficacy and safety of continued hydroxycarbamide therapy versus switching to ruxolitinib in patients with polycythaemia vera: a randomized, double-blind, double-dummy, symptom study (RELIEF).
abstract: The randomized, double-blind, double-dummy, phase 3b RELIEF trial evaluated polycythaemia vera (PV)-related symptoms in patients who were well controlled with a stable dose of hydroxycarbamide (also termed hydroxyurea) but reported PV-related symptoms. Patients were randomized 1:1 to ruxolitinib 10 mg BID (n = 54) or hydroxycarbamide (prerandomization dose/schedule; n = 56); crossover to ruxolitinib was permitted after Week 16. The primary endpoint, ≥50% improvement from baseline in myeloproliferative neoplasm -symptom assessment form total symptom score cytokine symptom cluster (TSS-C; sum of tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16, was achieved by 43·4% vs. 29·6% of ruxolitinib- and hydroxycarbamide-treated patients, respectively (odds ratio, 1·82; 95% confidence interval, 0·82-4·04; P = 0·139). The primary endpoint was achieved by 34% of a subgroup who maintained their hydroxycarbamide dose from baseline to Weeks 13-16. In a post hoc analysis, the primary endpoint was achieved by more patients with stable screening-to-baseline TSS-C scores (ratio ≤ 2) receiving ruxolitinib than hydroxycarbamide (47·4% vs. 25·0%; P = 0·0346). Ruxolitinib treatment after unblinding was associated with continued symptom score improvements. Adverse events were primarily grades 1/2 with no unexpected safety signals. Ruxolitinib was associated with a nonsignificant trend towards improved PV-related symptoms versus hydroxycarbamide, although an unexpectedly large proportion of patients who maintained their hydroxycarbamide dose reported symptom improvement.
authors.affiliation: Mayo Clinic Cancer Center, Scottsdale, AZ, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Mesa
authors.affiliation: Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, University of Florence, Florence, Italy.
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.affiliation: University of Kansas Medical Center, Westwood, KS, USA.
authors.forename: Abdulraheem
authors.initials: A
authors.lastname: Yacoub
authors.affiliation: ZNA Stuivenberg, Antwerp, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Zachee
authors.affiliation: Leicester Royal Infirmary, Leicester, UK.
authors.forename: Mamta
authors.initials: M
authors.lastname: Garg
authors.affiliation: Texas Oncology and US Oncology Research, San Antonio, TX, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Lyons
authors.affiliation: Department of Haematology, Oncology, Haemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Koschmieder
authors.affiliation: University of Lincoln and United Lincolnshire Hospital Trust, Lincoln, UK.
authors.forename: Ciro
authors.initials: C
authors.lastname: Rinaldi
authors.affiliation: Nottingham University Hospitals, Nottingham, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Byrne
authors.affiliation: Sandwell and West Birmingham Hospitals NHS Trust, West Bromwich, UK.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Hasan
authors.affiliation: University of Insubria, Varese, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Passamonti
authors.affiliation: University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Hunter
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Jones
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Huiling
authors.initials: H
authors.lastname: Zhen
authors.affiliation: Novartis Pharmaceuticals, East Hanover, NJ, USA.
authors.forename: Dany
authors.initials: D
authors.lastname: Habr
authors.affiliation: Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio Calabria, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Martino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018592:Cross-Over Studies; D004311:Double-Blind Method; D057915:Drug Substitution; D005221:Fatigue; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D011087:Polycythemia Vera / Q000188:drug therapy*; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D011788:Quality of Life; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D006918:Hydroxyurea
keywords: Janus kinase; hydroxycarbamide; polycythaemia vera; quality of life; signs and symptoms