Comparison of placebo and best available therapy for the treatment of myelofibrosis in the phase 3 COMFORT studies

Abstract

Prior to Janus kinase inhibitors, available therapies for myelofibrosis were generally supportive and did not improve survival. This analysis compares efficacy outcomes of patients with myelofibrosis in the control arms (placebo [n=154] and best available therapy [n=73]) from the two phase 3 COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment (COMFORT) studies. Spleen volume was assessed by magnetic resonance imaging/computed tomography at baseline and every 12 weeks through week 72; spleen length was assessed by palpation at each study visit. Health-related quality of life and symptoms were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items at baseline and in weeks 4, 8, 12, 16 and 24 in COMFORT-I and in weeks 8, 16, 24 and 48 in COMFORT-II. The demographic and baseline characteristics were similar between the control arms of the two studies. One patient who received placebo and no patients who received best available therapy had a ≥35% reduction in spleen volume from baseline at week 24. At 24 weeks, neither placebo nor best available therapy had produced clinically meaningful changes in global quality of life or symptom scales. Non-hematologic adverse events were mostly grade 1/2; the most frequently reported adverse events in each group were abdominal pain, fatigue, peripheral edema and diarrhea. These data suggest that non-Janus kinase inhibitor therapies provide little improvement in splenomegaly, symptoms or quality of life as compared with placebo. Both COMFORT-I (NCT00952289) and COMFORT-II (NCT00934544) studies have been appropriately registered with clinicaltrials.gov.

Figures

Figure 1.

Percent change from baseline in spleen volume as assessed by magnetic resonance imaging/computed tomography at week 24 for patients with baseline and ≥1 post-baseline assessment. BAT: best available therapy.

Figure 2.

Mean percentage change from baseline in (A) spleen volume as assessed by magnetic resonance imaging/computed tomography and (B) palpable spleen length over time. BAT: best available therapy.

Figure 3.

Mean change from baseline to week 24 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire-Core 30 Items (QLQ-C30) scores. Only patients with measurements at both baseline and week 24 were included. EORTC QLQ-C30 global health status/QoL and functioning scales range from 0 to 100, with higher scores indicating better health-related QoL. A clinically meaningful treatment difference was defined as a 10-point improvement or 10-point worsening from baseline for global health status/QoL. BAT: best available therapy.

Figure 4.

Mean change from baseline to week 24 in select European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core 30 Items (QLQ-C30) scores. EORTC QLQ-C30 symptom scales range from 0 to 100, with higher scores indicating worse symptoms. BAT: best available therapy. *n=105. **n=38. ***n=104.