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

Clin Lymphoma Myeloma Leuk. 2015 Apr;15(4):214-221.e1. doi: 10.1016/j.clml.2014.12.008. Epub 2014 Dec 27.

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.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Body Weight
  • Cholesterol / blood
  • Cholesterol / metabolism
  • Humans
  • Janus Kinases / antagonists & inhibitors
  • Nitriles
  • Organ Size
  • Primary Myelofibrosis / diagnosis
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / metabolism*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use*
  • Pyrimidines
  • Serum Albumin
  • Spleen / anatomy & histology
  • Spleen / pathology
  • Treatment Outcome

Substances

  • Biomarkers
  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • Serum Albumin
  • ruxolitinib
  • Cholesterol
  • Janus Kinases

Associated data

  • ClinicalTrials.gov/NCT00952289