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

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.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

CONSORT diagram illustrating the disposition of the 309 enrolled patients at the time of primary analysis data cutoff. (*) Three patients not evaluable for safety but included in the intent-to-treat analysis of efficacy.

Fig 2.

Individual symptom scores at baseline (in patients with symptoms at baseline) as measured by the modified Myelofibrosis Symptom Assessment Form v2.0. The most prevalent symptoms (reported in > 90% of patients in both treatment groups) and most severe symptoms were abdominal discomfort, early satiety, and inactivity. Scale range: 0, absent to 10, worst imaginable.

Fig 3.

(A-G) Assessment of individual symptom burden by using the modified Myelofibrosis Symptom Assessment Form v2.0. Individual symptom scores at each 4-week time point improved in patients receiving ruxolitinib, whereas patients who received placebo experienced a worsening of symptoms. P < .001 for all comparisons between ruxolitinib and placebo at all time points (weeks 4, 8, 12, 16, 20, and 24). Individual symptom scores at each 4-week time point were calculated by averaging the daily individual symptom scores from the previous 28 days.

Fig 4.

(A-F) Relationship between symptoms as assessed by the modified Myelofibrosis Symptom Assessment Form v2.0, with quality of life (QoL) as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at baseline. Patients receiving ruxolitinib who were categorized as ≥ 50% Total Symptom Score (TSS) responders achieved significantly greater improvements in the EORTC QLQ-C30 subscales versus patients in the placebo group.

Fig 5.

(A-F) Relationship between spleen volume reduction with ruxolitinib and patient-reported outcomes (PROs). Ruxolitinib-treated patients who achieved a ≥ 35% reduction in spleen volume experienced the greatest improvements in all PROs, whereas patients receiving placebo reported worsening of symptoms on these measures. However, patients given ruxolitinib who had ≥ 10% reduction in spleen volume also achieved significant improvements in all PROs. (D) Change from baseline in patient perception of their disease (baseline = score of 4 [no change]). PROMIS, Patient Reported Outcomes Measurement Information System; QoL, quality of life.