Overall survival with momelotinib vs. best available therapy in patients with ruxolitinib-experienced myelofibrosis: a matching-adjusted indirect comparison

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.