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

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.

• Authors: Ruben A Mesa, Jean-Jacques Kiladjian, Srdan Verstovsek, Haifa Kathrin Al-Ali, Jason Gotlib, Heinz Gisslinger, Richard Levy, Andres Siulnik, Vikas Gupta, Mahmudul Khan, John F DiPersio, Mari McQuitty, John V Catalano, Deborah S Hunter, Laurent Knoops, Michael Deininger, Francisco Cervantes, Carole Miller, Alessandro M Vannucchi, Richard T Silver, Tiziano Barbui, Moshe Talpaz, Giovanni Barosi, Elliott F Winton, Estella Mendeson, Jimmie H Harvey Jr, Murat O Arcasoy, Elizabeth Hexner, Roger M Lyons, Ronald Paquette, Azra Raza, William Sun, Victor Sandor, Hagop M Kantarjian, Claire Harrison
• Journal: Haematologica (Haematologica) Vol. 99 Issue 2 Pg. 292-8 (Feb 2014) ISSN: 1592-8721 [Electronic] Italy
• PMID: 23911705 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Kinase Inhibitors

Topics

• Adult
• Aged
• Aged, 80 and over
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Organ Size
• Primary Myelofibrosis (drug therapy, pathology, physiopathology)
• Protein Kinase Inhibitors (administration & dosage)
• Quality of Life
• Spleen (pathology, physiopathology)
• Splenomegaly (drug therapy, pathology, physiopathology)
• Time Factors