Efficacy of Momelotinib in Managing Anemia in Myelofibrosis: Results from the SIMPLIFY-2 Trial
Anemia significantly impacts patients with myelofibrosis, with many relying on ineffective red blood cell (RBC) transfusions. While JAK inhibitors like ruxolitinib may worsen anemia, momelotinib has shown promise in improving anemia and related symptoms. The SIMPLIFY-2 trial demonstrated momelotinib's benefits over best available therapy (BAT) in certain patient subgroups.
The trial was a multicenter, open-label, phase 3 study that randomized 156 patients (2:1) to receive momelotinib or BAT for 24 weeks. Conducted per the Declaration of Helsinki and Good Clinical Practice, the study included patients aged ≥ 18 with myelofibrosis requiring RBC transfusions or experiencing severe anemia while on ruxolitinib. Clinical assessments occurred biweekly, with spleen size measured every 12 weeks and daily symptom tracking via an electronic diary. The primary endpoint was spleen volume reduction (≥ 35%) at week 24, while secondary endpoints included total symptom score reduction and transfusion independence. Statistical analyses focused on specific patient subgroups defined by anemia status and transfusion requirements, with exploratory results summarized descriptively.
For the study, 156 patients were randomized, with 104 receiving momelotinib and 52 receiving BAT. The primary endpoint of spleen volume reduction (≥ 35%) at week 24 was not met (6.7% for momelotinib vs 5.8% for BAT). However, momelotinib showed significant benefits in secondary endpoints: 26.2% of patients achieved a total symptom score reduction (≥ 50%) compared to 5.9% in the BAT group (P = .0006), and 43.3% of momelotinib patients became transfusion-independent vs 21.2% in the BAT group (P = .0012).
Overall, the trial highlighted momelotinib's potential in improving anemia and related symptoms among patients who had previously received ruxolitinib. Although the primary endpoint of spleen volume reduction was not achieved, the significant improvements in total symptom score and transfusion independence underscore momelotinib's clinical relevance. The findings suggest that momelotinib may address unmet needs in anemia management, particularly for patients with moderate-to-severe anemia. The authors emphasize the importance of considering anemia as a critical factor in treatment decisions and suggest further studies to evaluate long-term benefits and potential integration of momelotinib into standard care for patients with myelofibrosis.
Reference
Harrison CN, Vannucchi AM, Recher C, et al. Momelotinib versus Continued Ruxolitinib or Best Available Therapy in JAK Inhibitor-Experienced Patients with Myelofibrosis and Anemia: Subgroup Analysis of SIMPLIFY-2. Adv Ther. 2024;41(9):3722-3735. doi: 10.1007/s12325-024-02928-4
