Comparison of placebo and best available therapy for the treatment of myelofibrosis in the phase 3 COMFORT studies

• Type of Material: Article
• Authors: Ruben A. Mesa, Mayo Clinic; Jean-Jacques Kiladjian, Hôpital Saint-Louis et Université Paris Diderot; Srdan Verstovsek, The University of Texas, MD Anderson Cancer Center; Haifa Kathrin Al-Ali, University of Leipzig; Jason Gotlib, Stanford Cancer Institute; Heinz Gisslinger, Medical University of Vienna; Richard Levy, Incyte Corporation; Andres Siulnik, Novartis Pharmaceuticals Corporation; Vikas Gupta, Emory University; Mahmudul Khan, Novartis Pharmaceuticals Corporation; John F. DiPersio, Washington University; Mari McQuitty, Novartis Pharmaceuticals Corporation; John V. Catalano, Frankston Hospital; Deborah S. Hunter, Incyte Corporation; Laurent Knoops, Université Catholique de Louvain; Michael Deininger, Oregon Health and Science University; Francisco Cervantes, Institut d’Investigacions Biomèdiques; Carole Miller, Saint Agnes Cancer Institute; Alessandro M. Vannucchi, University of Florence; Richard T. Silver, Weill Cornell Medical College; Tiziano Barbui, A.O. Ospedali Riuniti di Bergamo; Moshe Talpaz, University of Michigan; Giovanni Barosi, IRCCS Policlinico San Matteo Foundation; Elliot F. Mendeson, Novartis Pharmaceuticals Corporation; Elliott Winton, Emory University; Jimmie H. Harvey, Birmingham Hematology and Oncology; Murat O. Arcasoy, Duke University Health System; Elizabeth Hexner, University of Pennsylvania; Roger M. Lyons, Cancer Care Centers of South Texas; ROnald Paquette, University of California Los Angeles; Azra Raza, Columbia Presbyterian Medical Center; William Sun, Incyte Corporation; Victor Sandor, Incyte Corporation; Hagop M. Kantarjian, The University of Texas, MD Anderson Cancer Center; Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust
• Language: English
• Date: 2014-02-01
• Publisher: Ferrata Storti Foundation
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Ferrata Storti Foundation.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3324/haematol.2013.087650
• Title of Journal or Parent Work: Haematologica
• ISSN: 0390-6078
• Volume: 99
• Issue: 2
• Start Page: 292
• End Page: 298
• Grant/Funding Information: Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation.
• Keywords: Hematology; Science & Technology; MUTATION; QUALITY-OF-LIFE; RUXOLITINIB; BURDEN; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA-VERA; INTERNATIONAL WORKING GROUP; Life Sciences & Biomedicine; ESSENTIAL THROMBOCYTHEMIA; TYROSINE KINASE JAK2
• Research Categories: Health Sciences, General; Health Sciences, Medicine and Surgery

Abstract

Prior to Janus kinase inhibitors, available therapies for myelofibrosis were generally supportive and did not improve survival. This analysis compares efficacy outcomes of patients with myelofibrosis in the control arms (placebo [n=154] and best available therapy [n=73] ) from the two phase 3 COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment (COMFORT) studies. Spleen volume was assessed by magnetic resonance imaging/ computed tomography at baseline and every 12 weeks through week 72; spleen length was assessed by palpation at each study visit. Health-related quality of life and symptoms were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items at baseline and in weeks 4, 8, 12, 16 and 24 in COMFORT-I and in weeks 8, 16, 24 and 48 in COMFORT-II. The demographic and baseline characteristics were similar between the control arms of the two studies. One patient who received placebo and no patients who received best available therapy had a ≥35% reduction in spleen volume from baseline at week 24. At 24 weeks, neither placebo nor best available therapy had produced clinically meaningful changes in global quality of life or symptom scales. Non-hematologic adverse events were mostly grade 1/2; the most frequently reported adverse events in each group were abdominal pain, fatigue, peripheral edema and diarrhea. These data suggest that non-Janus kinase inhibitor therapies provide little improvement in splenomegaly, symptoms or quality of life as compared with placebo. Both COMFORT-I (NCT00952289) and COMFORT-II (NCT00934544) studies have been appropriately registered with clinicaltrials.gov.