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Leukemia. 2016 Aug;30(8):1701-7. doi: 10.1038/leu.2016.148. Epub 2016 May 23.

Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis.

Author information

1
Guy's and St Thomas' NHS Foundation Trust, Guy's Hospital, London, UK.
2
Center for Research and Innovation for Myeloproliferative Neoplasms-CRIMM, AOU Careggi, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
3
Hôpital Saint-Louis et Université Paris Diderot, Paris, France.
4
University of Leipzig, Leipzig, Germany.
5
Medical University of Vienna, Vienna, Austria.
6
Cliniques Universitaires Saint-Luc and de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
7
Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
8
Incyte Corporation, Wilmington, DE, USA.
9
Novartis Pharma, Basel, Switzerland.
10
Research Foundation, Ospedale Papa Giovanni XXIII, Bergamo, Italy.

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.

PMID:
27211272
PMCID:
PMC5399157
DOI:
10.1038/leu.2016.148
[Indexed for MEDLINE]
Free PMC Article

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