A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis
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- 1 March 2012
- journal article
- research article
- Published by Massachusetts Medical Society in The New England Journal of Medicine
- Vol. 366 (9), 799-807
- https://doi.org/10.1056/nejmoa1110557
Abstract
Ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and 2, has clinically significant activity in myelofibrosis. In this double-blind trial, we randomly assigned patients with intermediate-2 or high-risk myelofibrosis to twice-daily oral ruxolitinib (155 patients) or placebo (154 patients). The primary end point was the proportion of patients with a reduction in spleen volume of 35% or more at 24 weeks, assessed by means of magnetic resonance imaging. Secondary end points included the durability of response, changes in symptom burden (assessed by the total symptom score), and overall survival. The primary end point was reached in 41.9% of patients in the ruxolitinib group as compared with 0.7% in the placebo group (P<0.001). A reduction in spleen volume was maintained in patients who received ruxolitinib; 67.0% of the patients with a response had the response for 48 weeks or more. There was an improvement of 50% or more in the total symptom score at 24 weeks in 45.9% of patients who received ruxolitinib as compared with 5.3% of patients who received placebo (P<0.001). Thirteen deaths occurred in the ruxolitinib group as compared with 24 deaths in the placebo group (hazard ratio, 0.50; 95% confidence interval, 0.25 to 0.98; P=0.04). The rate of discontinuation of the study drug because of adverse events was 11.0% in the ruxolitinib group and 10.6% in the placebo group. Among patients who received ruxolitinib, anemia and thrombocytopenia were the most common adverse events, but they rarely led to discontinuation of the drug (in one patient for each event). Two patients had transformation to acute myeloid leukemia; both were in the ruxolitinib group. Ruxolitinib, as compared with placebo, provided significant clinical benefits in patients with myelofibrosis by reducing spleen size, ameliorating debilitating myelofibrosis-related symptoms, and improving overall survival. These benefits came at the cost of more frequent anemia and thrombocytopenia in the early part of the treatment period. (Funded by Incyte; COMFORT-I ClinicalTrials.gov number, NCT00952289.)Keywords
This publication has 17 references indexed in Scilit:
- Safety and Efficacy of INCB018424, a JAK1 and JAK2 Inhibitor, in MyelofibrosisNew England Journal of Medicine, 2010
- Splenic volume measurements on computed tomography utilizing automatically contouring software and its relationship with age, gender, and anthropometric parametersEuropean Journal of Radiology, 2010
- Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasmsBlood, 2010
- Molecular aspects of myeloproliferative neoplasmsInternational Journal of Hematology, 2010
- Regulation of myelopoiesis through syntenin-mediated modulation of IL-5 receptor outputBlood, 2009
- New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and TreatmentBlood, 2009
- Primary Myelofibrosis: Update on Definition, Pathogenesis, and TreatmentAnnual Review of Medicine, 2009
- JAKs in pathology: Role of Janus kinases in hematopoietic malignancies and immunodeficienciesSeminars in Cell & Developmental Biology, 2008
- Classification and diagnosis of myeloproliferative neoplasms: The 2008 World Health Organization criteria and point-of-care diagnostic algorithmsLeukemia, 2007
- International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT)Blood, 2006