Effect of ruxolitinib therapy on myelofibrosis-related symptoms and other patient-reported outcomes in COMFORT-I: a randomized, double-blind, placebo-controlled trial

J Clin Oncol. 2013 Apr 1;31(10):1285-92. doi: 10.1200/JCO.2012.44.4489. Epub 2013 Feb 19.

Abstract

Purpose: To assess the effects of ruxolitinib on symptom burden and quality of life (QoL) and to evaluate the ability of the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 to measure meaningful changes in myelofibrosis-related symptoms in patients with myelofibrosis.

Patients and methods: COMFORT-I (Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment-I) is a double-blind, placebo-controlled phase III study evaluating ruxolitinib in patients with intermediate-2 or high-risk myelofibrosis. Exploratory analyses were conducted on the following patient-reported outcomes (PROs) assessments: modified MFSAF v2.0 (individual symptoms and Total Symptom Score [TSS]), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale, and Patient Global Impression of Change (PGIC).

Results: Patients receiving ruxolitinib experienced improvements in individual myelofibrosis-related symptoms, although patients receiving placebo experienced worsening (P < .001). The majority (91%) of ruxolitinib-treated patients designated as ≥ 50% TSS responders (≥ 50% TSS improvement) self-reported their condition as either "Much improved" or "Very much improved" on the PGIC. These patients achieved significant improvements in the EORTC QLQ-C30 functional domains and Global Health Status/QoL versus patients receiving placebo, who experienced worsening on these measures (P ≤ .0135). Ruxolitinib-treated patients with a lesser degree of symptom improvement (< 50% TSS responders) also achieved improvements over placebo on these measures. The degree of spleen volume reduction with ruxolitinib correlated with improvements in TSS, PGIC, PROMIS Fatigue Scale, and EORTC Global Health Status/QoL. Ruxolitinib-treated patients who achieved a ≥ 35% reduction in spleen volume experienced the greatest improvements in these PROs.

Conclusion: Ruxolitinib-treated patients achieved clinically meaningful improvements in myelofibrosis-related symptoms and QoL, but patients receiving placebo reported worsening of symptoms and other PROs.

Trial registration: ClinicalTrials.gov NCT00952289.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia / chemically induced
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Fatigue / chemically induced
  • Humans
  • Janus Kinases / antagonists & inhibitors*
  • Nitriles
  • Primary Myelofibrosis / drug therapy
  • Primary Myelofibrosis / enzymology
  • Primary Myelofibrosis / pathology
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyrimidines
  • Quality of Life
  • Spleen / drug effects*
  • Spleen / pathology
  • Surveys and Questionnaires
  • Thrombocytopenia / chemically induced
  • Treatment Outcome

Substances

  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • Janus Kinases

Associated data

  • ClinicalTrials.gov/NCT00952289