title: Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I.
abstract: COMFORT-I is a randomized, double-blind, placebo-controlled trial of the Janus kinase 1/Janus kinase 2 inhibitor ruxolitinib in 309 patients with intermediate-2 or high-risk myelofibrosis. This analysis of COMFORT-I describes the long-term efficacy and safety of ruxolitinib (median follow-up, 2 years). Spleen volume was measured by magnetic resonance imaging, and quality of life was evaluated using the EORTC QLQ-C30. Overall survival was determined according to randomized treatment group. At the time of this analysis, 100 of 155 patients randomized to ruxolitinib were still receiving treatment. All patients randomized to placebo crossed over to ruxolitinib or discontinued within 3 months of the primary analysis (median time to crossover, 41 weeks). Mean spleen volume reductions in the ruxolitinib group were 31.6% at week 24 and 34.9% at week 96; improvements in quality of life measures were also maintained. Improved survival was observed for ruxolitinib (n=27 deaths) versus placebo (n=41 deaths) (hazard ratio=0.58; 95% confidence interval: 0.36, 0.95; P=0.03). The incidence of new-onset grade 3 or 4 anemia and thrombocytopenia decreased over time to levels observed in patients receiving placebo. These data indicate that ruxolitinib treatment provides durable reductions in spleen volume and improvements in quality of life and suggest a continued survival advantage for ruxolitinib over placebo.
authors.affiliation: sverstov@mdanderson.org.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Mesa
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
authors.forename: Richard S
authors.initials: RS
authors.lastname: Levy
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
authors.forename: John V
authors.initials: JV
authors.lastname: Catalano
authors.forename: Michael W N
authors.initials: MW
authors.lastname: Deininger
authors.forename: Carole B
authors.initials: CB
authors.lastname: Miller
authors.forename: Richard T
authors.initials: RT
authors.lastname: Silver
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.forename: Elliott F
authors.initials: EF
authors.lastname: Winton
authors.forename: Jimmie H
authors.initials: JH
authors.lastname: Harvey
authors.forename: Murat O
authors.initials: MO
authors.lastname: Arcasoy
authors.forename: Elizabeth O
authors.initials: EO
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: Kris
authors.initials: K
authors.lastname: Vaddi
authors.forename: Susan
authors.initials: S
authors.lastname: Erickson-Viitanen
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
mesh_terms: D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
chemical_list: D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053612:Janus Kinases
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