SynthesisAnnals of hematology2026
Overall survival with momelotinib vs. best available therapy in patients with ruxolitinib-experienced myelofibrosis: a matching-adjusted indirect comparison.
Synthesis in Annals of hematology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The Janus kinase (JAK) inhibitor ruxolitinib is a standard first-line therapy for patients with symptomatic and/or intermediate- to high-risk myelofibrosis (MF). However, the majority of patients discontinue ruxolitinib within 5 years of initiation, mainly due to lack or loss of response and/or therapy-related cytopenias. Additional treatments are needed to improve long-term outcomes, including overall survival (OS). Momelotinib, a JAK1/JAK2/activin A receptor type 1 inhibitor, has demonstrated benefits in reducing anemia and improving symptoms and spleen size in 3 phase 3 trials of patients with intermediate- to high-risk MF (SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM). These studies also provide data on patients who received momelotinib after discontinuing ruxolitinib. In the absence of long-term head-to-head comparisons of momelotinib and other treatments after discontinuation of ruxolitinib, the present study compared OS in patients with ruxolitinib-experienced MF from the momelotinib phase 3 trials vs. those treated with best available therapy (BAT) after ruxolitinib from the RUX-MF retrospective real-world study. The comparison was performed using an unanchored matching-adjusted indirect comparison (MAIC). Additionally, an MAIC of OS was conducted in an anemic subgroup (hemoglobin < 10 g/dL). After adjustment for cross-trial differences, the MAIC results showed a favorable trend for momelotinib vs. BAT, both in the overall population and in the anemic subgroup, with hazard ratios < 1 across all analytical scenarios and all population-matching models with an effective sample size of ≥ 20. This study is a key addition to current evidence surrounding OS post ruxolitinib and highlights the benefit of momelotinib in this setting.
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