The clinical benefit of ruxolitinib across patient subgroups: analysis of a placebo-controlled, Phase III study in patients with myelofibrosis

• Authors: Srdan Verstovsek, The University of Texas MD Anderson Cancer Center, Houston; Ruben A. Mesa, Mayo Clinic; Jason Gotlib, Stanford Cancer Institute; Richard S. Levy, Incyte Corporation; Vikas Gupta, Emory University; John F. DiPersio, Washington University School of Medicine; John V. Catalano, Frankston Hospital; Michael Deininger, Oregon Health and Science University; Carole Miller, Saint Agnes Cancer Institute; Richard T. Silver, Weill Cornell Medical College; Moshe Talpaz, University of Michigan; Elliott F Winton, Emory University; Jimmie H. Harvey, Birmingham Hematology & Oncology,; Murat O. Arcasoy, Duke Cancer Institute; Elizabeth Hexner, University of Pennsylvania; Roger M. Lyons, Cancer Care Centers of South Texas/US Oncology; Ronald Paquette, UCLA Medical 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, The University of Texas MD Anderson Cancer Center, Houston,
• Journal Title: British Journal of Haematology
• Volume: Volume 161, Number 4
• Publisher: Wiley | 2013-05-01, Pages 508-516
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1111/bjh.12274
• Subjects: Health Sciences, Pharmacology; Health Sciences, Epidemiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Hematology; Myelofibrosis; ruxolitinib; subgroups; spleen volume; symptoms; INTERNATIONAL WORKING GROUP; WORLD-HEALTH-ORGANIZATION; MYELOPROLIFERATIVE NEOPLASMS; CRITERIA; CLASSIFICATION; DIAGNOSIS

Abstract

Myelofibrosis (MF) patients can present with a wide spectrum of disease characteristics. We analysed the consistency of ruxolitinib efficacy across patient subgroups in the COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment (COMFORT-I,) a double-blind trial, where patients with intermediate-2 or high-risk MF were randomized to twice-daily oral ruxolitinib (n=155) or placebo (n=154). Subgroups analysed included MF subtype (primary, post-polycythaemia vera, post-essential thrombocythaemia), age (≤65, > 65years), International Prognostic Scoring System risk group, baseline Eastern Cooperative Oncology Group performance status (0, 1, ≥2), JAK2 V617F mutation (positive, negative), baseline haemoglobin level (≥100, < 100g/l), baseline platelet count (100-200×10 9 /l, > 200×10 9 /l), baseline palpable spleen size (≤10, > 10cm), and baseline quartile of spleen volume and Total Symptom Score (TSS; Q1=lowest, Q4=highest). Mean percentage change from baseline to week 24 in spleen volume and TSS were calculated for ruxolitinib and placebo in each subgroup. Overall survival was estimated by Kaplan-Meier method according to original randomization group. In ruxolitinib-treated patients, reductions in spleen volume and TSS and evidence of improved survival relative to placebo across subgroups were consistent with those seen in the COMFORT-I population, confirming that ruxolitinib is an effective therapy for the spectrum of MF patients studied in COMFORT-I.