title: Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I.
abstract: In the phase III COMFORT-I study, the Janus kinase 1 (JAK1)/JAK2 inhibitor ruxolitinib provided significant improvements in splenomegaly, key symptoms, and quality-of-life measures and was associated with an overall survival benefit relative to placebo in patients with intermediate-2 or high-risk myelofibrosis. This planned analysis assessed the long-term efficacy and safety of ruxolitinib at a median follow-up of 149 weeks. At data cutoff, approximately 50% of patients originally randomized to ruxolitinib remained on treatment whereas all patients originally assigned to placebo had discontinued or crossed over to ruxolitinib. At week 144, mean spleen volume reduction was 34% with ruxolitinib. Previously observed improvements in quality-of-life measures were sustained with longer-term ruxolitinib therapy. Overall survival continued to favor ruxolitinib despite the majority of placebo patients crossing over to ruxolitinib [hazard ratio 0.69 (95% confidence interval: 0.46-1.03); P = 0.067]. Exploratory analyses suggest that crossover may have contributed to an underestimation of the true survival difference between the treatment groups. Ruxolitinib continued to be generally well tolerated; there was no pattern of worsening grade ≥ 3 anemia or thrombocytopenia with longer-term ruxolitinib exposure. These longer-term data continue to support the efficacy and safety of ruxolitinib in patients with myelofibrosis. The study is registered at clinicaltrials.gov: NCT00952289.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA sverstov@mdanderson.org.
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
authors.affiliation: Mayo Clinic, Scottsdale, AZ, USA.
authors.forename: Ruben A
authors.initials: RA
authors.lastname: Mesa
authors.affiliation: Stanford Cancer Institute, Stanford, CA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Levy
authors.affiliation: Princess Margaret Cancer Center, University of Toronto, ON, Canada.
authors.forename: Vikas
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: DiPersio
authors.affiliation: Frankston Hospital and Department of Clinical Haematology, Monash University, Frankston, Australia.
authors.forename: John V
authors.initials: JV
authors.lastname: Catalano
authors.affiliation: *Oregon Health and Science University, Portland, OR, USA.
authors.forename: Michael W N
authors.initials: MW
authors.lastname: Deininger
authors.affiliation: Saint Agnes Cancer Institute, Baltimore, MD, USA.
authors.forename: Carole B
authors.initials: CB
authors.lastname: Miller
authors.affiliation: Weill Cornell Medical Center, New York, NY, USA.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Silver
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: Moshe
authors.initials: M
authors.lastname: Talpaz
authors.affiliation: Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Elliott F
authors.initials: EF
authors.lastname: Winton
authors.affiliation: Birmingham Hematology and Oncology, Birmingham, AL, USA.
authors.forename: Jimmie H
authors.initials: JH
authors.lastname: Harvey
authors.affiliation: Duke University Health System, Durham, NC, USA.
authors.forename: Murat O
authors.initials: MO
authors.lastname: Arcasoy
authors.affiliation: Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Elizabeth O
authors.initials: EO
authors.lastname: Hexner
authors.affiliation: Cancer Care Centers of South Texas/US Oncology, San Antonio, TX, USA.
authors.forename: Roger M
authors.initials: RM
authors.lastname: Lyons
authors.affiliation: Columbia Presbyterian Medical Center, New York, NY, USA.
authors.forename: Azra
authors.initials: A
authors.lastname: Raza
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Kris
authors.initials: K
authors.lastname: Vaddi
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: William
authors.initials: W
authors.lastname: Sun
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Sandor
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
mesh_terms: D005500:Follow-Up Studies; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D009570:Nitriles; D009929:Organ Size / Q000187:drug effects; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000401:mortality*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053612:Janus Kinases