Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I

• Type of Material: Article
• Authors: Srdan Verstovsek, University of Texas M.D. Anderson Cancer Center; Ruben A. Mesa, Mayo Clinic; Jason Gotlib, Stanford Cancer Institute; Richard S. Levy, Incyte Corporation; Vikas Gupta, Emory University; John F. DiPersio, Washington University; John V. Catalano, Monash University; Michael W. N. Deininger, University of Utah; Carole B. Miller, Saint Agnes Cancer Institute; Richard T. Silver, Weill Cornell Medical Center; Moshe Talpaz, University of Michigan; Elliott Winton, Emory University; Jimmie H. Harvey, Birmingham Hematology and Oncology; Murat O. Arcasoy, Duke University Health System; Elizabeth O. Hexner, University of Pennsylvania; Roger M. Lyons, Cancer Care Centers of South Texas/US Oncology; Ronald Paquette, UCLA Division of Hematology/Oncology; Azra Raza, Columbia Presbyterian Medical Center; Kris Vaddi, Incyte Corporation; Susan Erickson-Viitanen, Incyte Corporation; William Sun, Incyte Corporation; Victor Sandor, Incyte Corporation; Hagop M. Kantarjian, University of Texas M.D. Anderson Cancer Center
• Language: English
• Date: 2013-12-01
• Publisher: Ferrata Storti Foundation
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Ferrata Storti Foundation.
• Final Published Version (URL): http://dx.doi.org/10.3324/haematol.2013.092155
• Title of Journal or Parent Work: Haematologica
• ISSN: 0390-6078
• Volume: 98
• Issue: 12
• Start Page: 1865
• End Page: 1871
• Grant/Funding Information: COMFORT-I was supported by Incyte Corporation.
• Keywords: Life Sciences & Biomedicine; THERAPY; Hematology; DOUBLE-BLIND; PLACEBO-CONTROLLED TRIAL; MYELOPROLIFERATIVE NEOPLASMS; Science & Technology
• Research Categories: Health Sciences, Oncology

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.