MF symptoms following an immediate switch from ruxolitinib to momelotinib

In this video, Dr Jan Brijs, hematologist at AZ Delta (Roeselare, Belgium), discusses a post hoc analysis of the phase 3 SIMPLIFY-1 and SIMPLIFY-2 trials presented at the 2026 European Hematology Association (EHA) Congress, evaluating the safety of immediate transition from ruxolitinib to momelotinib in patients with myelofibrosis without dose tapering or a washout period.

Although ruxolitinib effectively reduces splenomegaly and disease-related symptoms, treatment discontinuation may precipitate ruxolitinib discontinuation syndrome (RDS), characterized by worsening constitutional symptoms, splenomegaly, hematologic abnormalities, hemodynamic instability and, in severe cases, a cytokine release syndrome-like hyperinflammatory state. The analysis therefore examined whether an immediate switch to momelotinib could be performed safely without increasing the risk of RDS.

In SIMPLIFY-1, 197 patients directly switched from ruxolitinib to momelotinib after 24 weeks of treatment. Overall, 88 patients experienced adverse events after crossover, of whom 21 patients (11%) developed events resembling myelofibrosis or RDS (e.g., fatigue, dizziness, pruritus and headache). Nearly all events were low grade, with only two cases of grade 3 fatigue. Symptoms occurred predominantly during the first two weeks after transition, with the incidence of new events declining to less than 5% during weeks 3–4 and to less than 3% during weeks 5–6. Approximately 50% of fatigue, pruritus and night sweats, and 90% of dizziness cases resolved either spontaneously or with medical management.

The SIMPLIFY-2 analysis included 75 JAK inhibitor-experienced patients who had received ruxolitinib for at least 12 weeks before directly switching to momelotinib. Most patients demonstrated an improvement in myelofibrosis Total Symptom Score and individual symptom domains following crossover, with no evidence of symptom worsening suggestive of RDS. Although limited by the relatively small patient numbers and the use of clinical trial rather than real-world data, the findings support immediate switching from ruxolitinib to momelotinib without tapering or a washout period, with adverse events being uncommon, predominantly low grade, transient and manageable.