title: Comparison of placebo and best available therapy for the treatment of myelofibrosis in the phase 3 COMFORT studies.
abstract: Prior to Janus kinase inhibitors, available therapies for myelofibrosis were generally supportive and did not improve survival. This analysis compares efficacy outcomes of patients with myelofibrosis in the control arms (placebo [n=154] and best available therapy [n=73]) from the two phase 3 COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment (COMFORT) studies. Spleen volume was assessed by magnetic resonance imaging/computed tomography at baseline and every 12 weeks through week 72; spleen length was assessed by palpation at each study visit. Health-related quality of life and symptoms were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items at baseline and in weeks 4, 8, 12, 16 and 24 in COMFORT-I and in weeks 8, 16, 24 and 48 in COMFORT-II. The demographic and baseline characteristics were similar between the control arms of the two studies. One patient who received placebo and no patients who received best available therapy had a ≥35% reduction in spleen volume from baseline at week 24. At 24 weeks, neither placebo nor best available therapy had produced clinically meaningful changes in global quality of life or symptom scales. Non-hematologic adverse events were mostly grade 1/2; the most frequently reported adverse events in each group were abdominal pain, fatigue, peripheral edema and diarrhea. These data suggest that non-Janus kinase inhibitor therapies provide little improvement in splenomegaly, symptoms or quality of life as compared with placebo. Both COMFORT-I (NCT00952289) and COMFORT-II (NCT00934544) studies have been appropriately registered with clinicaltrials.gov.
authors.affiliation: claire.harrison@gstt.nhs.uk.
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Mesa
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Kiladjian
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Haifa Kathrin
authors.initials: HK
authors.lastname: Al-Ali
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
authors.forename: Heinz
authors.initials: H
authors.lastname: Gisslinger
authors.forename: Richard
authors.initials: R
authors.lastname: Levy
authors.forename: Andres
authors.initials: A
authors.lastname: Siulnik
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
authors.forename: Mahmudul
authors.initials: M
authors.lastname: Khan
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
authors.forename: Mari
authors.initials: M
authors.lastname: McQuitty
authors.forename: John V
authors.initials: JV
authors.lastname: Catalano
authors.forename: Deborah S
authors.initials: DS
authors.lastname: Hunter
authors.forename: Laurent
authors.initials: L
authors.lastname: Knoops
authors.forename: Michael
authors.initials: M
authors.lastname: Deininger
authors.forename: Francisco
authors.initials: F
authors.lastname: Cervantes
authors.forename: Carole
authors.initials: C
authors.lastname: Miller
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: Richard T
authors.initials: RT
authors.lastname: Silver
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barosi
authors.forename: Elliott F
authors.initials: EF
authors.lastname: Winton
authors.forename: Estella
authors.initials: E
authors.lastname: Mendeson
authors.forename: Jimmie H
authors.initials: JH
authors.lastname: Harvey
authors.forename: Murat O
authors.initials: MO
authors.lastname: Arcasoy
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hexner
authors.forename: Roger M
authors.initials: RM
authors.lastname: Lyons
authors.forename: Ronald
authors.initials: R
authors.lastname: Paquette
authors.forename: Azra
authors.initials: A
authors.lastname: Raza
authors.forename: William
authors.initials: W
authors.lastname: Sun
authors.forename: Victor
authors.initials: V
authors.lastname: Sandor
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Claire
authors.initials: C
authors.lastname: Harrison
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011788:Quality of Life; D013154:Spleen / Q000473:pathology / Q000503:physiopathology; D013163:Splenomegaly / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D047428:Protein Kinase Inhibitors
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