title: Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis.
abstract: Ruxolitinib is a Janus kinase (JAK) (JAK1/JAK2) inhibitor that has demonstrated superiority over placebo and best available therapy (BAT) in the Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment (COMFORT) studies. COMFORT-II was a randomized (2:1), open-label phase 3 study in patients with myelofibrosis; patients randomized to BAT could crossover to ruxolitinib upon protocol-defined disease progression or after the primary end point, confounding long-term comparisons. At week 48, 28% (41/146) of patients randomized to ruxolitinib achieved ⩾35% decrease in spleen volume (primary end point) compared with no patients on BAT (P<0.001). Among the 78 patients (53.4%) in the ruxolitinib arm who achieved ⩾35% reductions in spleen volume at any time, the probability of maintaining response was 0.48 (95% confidence interval (CI), 0.35-0.60) at 5 years (median, 3.2 years). Median overall survival was not reached in the ruxolitinib arm and was 4.1 years in the BAT arm. There was a 33% reduction in risk of death with ruxolitinib compared with BAT by intent-to-treat analysis (hazard ratio (HR)=0.67; 95% CI, 0.44-1.02; P=0.06); the crossover-corrected HR was 0.44 (95% CI, 0.18-1.04; P=0.06). There was no unexpected increased incidence of adverse events with longer exposure. This final analysis showed that spleen volume reductions with ruxolitinib were maintained with continued therapy and may be associated with survival benefits.
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust, Guy's Hospital, London, UK.
authors.forename: C N
authors.initials: CN
authors.lastname: Harrison
authors.affiliation: Center for Research and Innovation for Myeloproliferative Neoplasms-CRIMM, AOU Careggi, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: A M
authors.initials: AM
authors.lastname: Vannucchi
authors.affiliation: Hôpital Saint-Louis et Université Paris Diderot, Paris, France.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Kiladjian
authors.affiliation: University of Leipzig, Leipzig, Germany.
authors.forename: H K
authors.initials: HK
authors.lastname: Al-Ali
authors.affiliation: Medical University of Vienna, Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Gisslinger
authors.affiliation: Cliniques Universitaires Saint-Luc and de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Knoops
authors.affiliation: Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Cervantes
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Jones
authors.affiliation: Incyte Corporation, Wilmington, DE, USA.
authors.forename: K
authors.initials: K
authors.lastname: Sun
authors.affiliation: Novartis Pharma, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: McQuitty
authors.affiliation: Novartis Pharma, Basel, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Stalbovskaya
authors.affiliation: Novartis Pharma, Basel, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Gopalakrishna
authors.affiliation: Research Foundation, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Barbui
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018592:Cross-Over Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D009929:Organ Size / Q000187:drug effects; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000401:mortality; D011720:Pyrazoles / Q000008:administration & dosage*; D011743:Pyrimidines; D013154:Spleen; D015996:Survival Rate
chemical_list: D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib