Effects of ruxolitinib treatment on metabolic and nutritional parameters in patients with myelofibrosis from COMFORT-I

Abstract

Background: In the COMFORT (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy)-I study, the Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib provided significant reductions in splenomegaly, improvements in myelofibrosis (MF)-related symptoms, and a survival advantage relative to placebo in patients with intermediate-2 or high-risk MF. In this post hoc analysis, we assessed the effects of ruxolitinib treatment on measures of metabolic and nutritional status.

Patients and methods: Patients were randomized to receive ruxolitinib (n = 155; 15 or 20 mg twice a day for patients with baseline platelet counts of 100-200 × 10(9)/L or > 200 × 10(9)/L, respectively) or placebo (n = 154). The primary end point was the proportion of patients with a ≥ 35% spleen volume reduction from baseline to week 24. A secondary end point was the proportion of patients with ≥ 50% improvement in Total Symptom Score (TSS) from baseline to week 24, measured using the modified Myelofibrosis Symptom Assessment Form version 2.0. Weight, cholesterol, and albumin were measured at specified time points throughout the study.

Results: Compared with placebo, ruxolitinib treatment was associated with increased weight (mean change: 3.9 kg vs. -1.9 kg), total cholesterol (mean percentage change: 26.4% vs. -3.3%), and albumin levels (mean percentage change: 5.8% vs. -1.7%) at week 24; sustained improvements were observed with longer-term ruxolitinib therapy. Relative to placebo, increases in mean weight, total cholesterol, and albumin levels were observed with ruxolitinib treatment regardless of the degree of spleen volume and TSS reductions at 24 weeks.

Conclusion: Treatment with ruxolitinib improved measures of metabolic and nutritional status of patients with intermediate-2 or high-risk MF.

Trial registration: ClinicalTrials.gov NCT00952289.

Keywords: Albumin; Cachexia; Cholesterol; JAK inhibitor; Weight.

Conflict of interest statement

Conflicts of Interest

Dr Mesa has received research funding from Genentech, Gilead, Incyte, Lilly, NS Pharma, Sanofi-Aventis, and YM Biosciences. Dr Verstovsek has received research funding from AstraZeneca, Bristol Myers Squibb, Celgene, Cell Therapeutics, Inc., Geron, Gilead, Incyte, Infinity Pharmaceuticals, Lilly Oncology, NS Pharma, Promedior, Roche, Seattle Genetics, and Galena. Dr Gupta has served as a consultant/advisory board member for Incyte and Novartis and has received research funding from Incyte, and Novartis through his institution. Dr Mascarenhas has served as a consultant for Incyte and has received clinical trial support from Incyte, Novartis, and Roche. Dr Atallah has served as a consultant for and has received research funding from Incyte Corporation. Drs Burn, Sun, and Sandor are employees of Incyte Corporation and have equity ownership. Dr Gotlib has served on an advisory committee and has received research funding and travel support from Incyte Corporation.

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Mean Change in Body Weight (A), Total Cholesterol (B), and Albumin (C) Over Time in Patients Receiving Ruxolitinib or Placebo Vertical lines indicate the standard error of the mean.

Figure 2

Mean Percentage Change From Baseline in Body Weight in Ruxolitinib-Treated Patients by Week 24 Spleen Volume Reduction Group Vertical lines indicate the standard error of the mean.

Figure 3

Mean Percentage Change From Baseline in Body Weight in Ruxolitinib-Treated Patients by Week 24 Total Symptom Score Reduction Group Vertical lines indicate the standard error of the mean.

Figure 4

Hierarchical Clustering of Plasma Markers With Changes in Weight Alone (top), Changes in Total Cholesterol Alone (middle), or Changes in Albumin Alone (bottom) Red denotes increases at week 24 relative to baseline. Green denotes decreases at week 24 relative to baseline. Owing to differences in the magnitude of changes between markers, the heat map color intensities were normalized.