Ruxolitinib in Patients with Myelofibrosis

Chicago—A phase 3 trial found that ruxolitinib showed a clinical benefit in reducing spleen size and significantly improved disease-related symptoms, functioning, and quality of life in patients with myelofibrosis compared with the best available therapy (BAT). Alessandro Vannuchi, MD, the study’s coauthor, presented the results in an oral abstract session at the ASCO meeting. The randomized, multicenter, open-label COMFORT-II (Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment) study continued the positive results of ruxolitinib, which proved superior to placebo in the randomized, double-blind, placebo-controlled COMFORT-I trial. COMFORT-II had a longer end point than COMFORT-I. Dr. Vannuchi said the COMFORT trials are the first randomized studies to examine the treatment of myelofibrosis, an incurable bone marrow disorder with progressive disabling symptoms and spleen enlargement. In COMFORT-II, the authors enrolled 219 patients at 56 sites in 9 European countries who had primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis with ≥2 International Prognostic Scoring System risk factors. There were 73 patients who received the BAT and 146 patients who received 15- or 20-mg twice-daily doses of ruxolitinib, a Janus kinase inhibitor. Patients were allowed to cross over or enter an extension phase if they had a splenectomy or progressive splenomegaly, which was defined as a 25% increase in spleen volume compared with the on-study nadir. There were 18 patients (25%) in the BAT group who crossed over to ruxolitinib. The primary end point was the proportion of patients who had a ≥35% reduction in spleen volume through week 48 as measured by a magnetic resonance imaging examination. The main secondary end point was the percentage of patients who had a ≥35% reduction in spleen volume through week 24. Baseline demographics were similar between the groups. The average age was approximately 66 years, while approximately 57% were males. Two thirds of the patients in the BAT arm received ≥1 medications. The most common treatments were antineoplastic agents (51% of patients), hydroxyurea (47% of patients), and glucocorticoids (16% of patients). At 48 weeks, 28.5% of patients in the ruxolitinib group reached the primary end point compared with 0% in the BAT group (P<.0001). After 24 weeks, 31.9% of patients receiving ruxolitinib reached the main secondary end point compared with none in the BAT group (P<.0001). The median time to response was 12.29 weeks. In addition, 44 of the 69 patients (64%) who had a ≥35% reduction in spleen volume achieved the reduction at the first assessment (after 12 weeks). Furthermore, 97% of patients who received ruxolitinib had a decrease in spleen volume compared with 56% of patients who received the BAT (P<.0001). There were no significant differences in the groups in terms of progression-free survival, leukemia-free survival, or overall survival. Of the patients who took ruxolitinib, 42% had grade 3 or 4 anemia compared with 31% in the BAT arm. However, the percentages of patients with a reduction in platelet counts were nearly identical (8% in the ruxolitinib group vs 7% in the BAT group). Dr. Vannuchi said the adverse events were similar in the groups and that ruxolitinib has an acceptable safety profile. In the BAT group, 33% of patients discontinued treatment compared with 18% of patients in the ruxolitinib group, although the percentage of patients in each group who discontinued because of adverse events was similar (ruxolitinib 8% vs BAT 5%).