Momelotinib vs Ruxolitinib for Myelofibrosis: Phase 3 Trial Yields Mixed Results
Researchers compared the safety and efficacy of ruxolitinib vs momelotinib, a selective JAK1/2 inhibitor, among JAK inhibitor–naïve patients with myelofibrosis.
Among patients with myelofibrosis, momelotinib is inferior to ruxolitinib for total symptom score (TSS) reduction, but not for spleen-volume reduction, according to an article published in the Journal of Clinical Oncology.1
Myelofibrosis is a hematological condition that involves abnormal bone marrow activity and, while often asymptomatic, can lead to enlarged spleen size, anemia, and other symptoms. Among 90% of patients, hyperactive Janus kinase (JAK)-signaling activity can be detected. Ruxolitinib, a JAK inhibitor, is the only treatment for myelofibrosis approved in the United States.
For the randomized, phase 3, non-inferiority SIMPLIFY-1 trial (ClinicalTrials.gov Identifier: NCT01969838), researchers compared the safety and efficacy of ruxolitinib vs momelotinib, a selective JAK1/2 inhibitor, among JAK inhibitor–naïve patients with myelofibrosis. The primary endpoint was spleen-volume reduction of at least 35%; secondary endpoints included TSS reduction of at least 50% and the proportion of patients who remained transfusion-independent at week 24 of treatment.
Of 432 enrolled patients, 376 completed the planned double-blind phase of 24 weeks (175 patients with momelotinib and 201 with ruxolitinib), representing an 18.6% discontinuation rate for momelotinib and 7.4% for ruxolitinib. Baseline characteristics were similar in both groups.
All 432 originally enrolled patients were included in the final analysis at week 24 (215 patients in the momelotinib group and 217 for ruxolitinib). Momelotinib was non-inferior to ruxolitinib for the primary endpoint of 35% or greater spleen-volume reduction (26.5% vs 29%, respectively; P = .011), but not for 50% or greater TSS reduction (28.4% vs 42.2%; P = .98).
Patients who received momelotinib were, however, more likely to be transfusion-independent at week 24 (66.5% vs 49.3% for ruxolitinib).
The most frequent treatment-related adverse events in both groups were thrombocytopenia and anemia, both of which were more common in the ruxolitinib group (29.2% and 38%, respectively) vs the momelotinib group (18.7% and 13.6%, respectively). Seven percent of patients in the momelotinib group and 3% of patients in the ruxolitinib group had grade 3 or worse infections.
The authors concluded that, given these mixed results, “treatment decisions might also consider these tradeoffs, should momelotinib gain approval for this indication.”
- Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: A phase III randomized trial of momelotinib versus ruxolitinib in Janus kinase inhibitor–naïve patients with myelofibrosis. J Clin Oncol. 2017 Sep 20. doi: 10.1200/JCO.2017.73.4418 [Epub ahead of print]