Practical Measures of Clinical Benefit With Ruxolitinib Therapy: An Exploratory Analysis of COMFORT-I

Abstract

Background: The phase III COMFORT (Controlled Myelofibrosis Study With Oral JAK inhibitor Treatment)-I and COMFORT-II trials in patients with intermediate-2 or high-risk myelofibrosis (MF) showed that ruxolitinib was superior to placebo and best available therapy, respectively, for improvements in spleen volume, MF-related symptoms, and overall survival (OS). However, patients managed in community settings might not have access to the methods used in the COMFORT trials. In this exploratory analysis we summarize efficacy findings of COMFORT-I using practical, community-oriented measures of patient outcomes.

Patients and methods: In this post hoc analysis of data from COMFORT-I we evaluated changes from baseline to week 12 in spleen size (palpable length and volume), patient-reported outcomes (Patient Global Impression of Change; Myelofibrosis Symptom Assessment Form; Patient-Reported Outcomes Measurement System Fatigue Scale), body weight, and serum albumin levels in 5 subgroups of ruxolitinib-treated patients on the basis of week 12 spleen length changes from baseline: (1-4) ≥ 50%, 25% to < 50%, 10% to < 25%, or < 10% reduction; and (5) worsening. OS was evaluated in ruxolitinib-treated patients with week 12 spleen length reductions from baseline ≥ 50%, 25% to < 50%, or < 25% (including worsening).

Results: In all spleen length subgroups, including patients with worsening spleen length at week 12, ruxolitinib (n = 150) was associated with improvements in spleen volume, patient-reported symptom burden, body weight, and serum albumin levels. Greater reductions in spleen length were associated with prolonged OS.

Conclusion: A variety of assessment methods beyond palpable spleen length that are easily accessible in the community setting might be useful in evaluating the clinical benefit of ruxolitinib over time in patients with MF.

Trial registration: ClinicalTrials.gov NCT00952289.

Keywords: Community hospitals; Janus kinases; Myelofibrosis; Myeloproliferative disorders; Splenomegaly.

Figure 1

Change From Baseline in Spleen Size. (A) Mean Percentage Change From Baseline to Week 12 in Spleen Length and Spleen Volume. (B) Mean (SE) Percentage Change From Baseline in Spleen Volume Over Time *1 Patient Did Not Have an Evaluable Spleen Volume Assessement and Was Excluded From the Spleen Volume Calculation. ^†2 patients Did Not Have Evaluable Spleen Volume Assessments and Were Excluded From the Spleen Volume Calculation

Figure 2

Proportion of Patients Reporting “Much Improved” or “Very Much Improved” on the PGIC at Week 12 Abbreviation: PGIC = Patient Global Impression of Change

Figure 3

Mean Percentage Change From Baseline to Week 12 MFSAF TSS and Individual Symptom Score. The Number of Evaluable patients in Each Group Ranged as Follows. Ruxolitinib: ≥ 50% Reduction, 40 to 53; 25% to < 50% Reduction, 34 to 41; 10% to < 25% Reduction,14 to 21;<10% Reduction, 9 to 15; Worsening , 6 to 9; Placebo: 97 to 129 Abbreviations: MFSAF = Myelofibrosis Symptom Assessment Form; TSS = total symptom score.

Figure 4

Mean Change From Baseline to Week 12 in PROMIS Fatigue Scale Score Abbreviation: PROMIS = Patient-Reported Outcomes Measurement System.

Figure 5

Mean Change From Baseline to Week 12 Metabolic Measures Assessed Measures Were (A) Body Weight and (B) Serum Albumin

Figure 6

Overall Survial. Patients in the Ruxolitinib Group Were Analyzed in 3 Subgroups on the Basis of Reduction From Baseline in Spleen Length at Week 12: ≥ 50% 25% to 50% , and < 25% (including Woresening Spleen Length)