Real-World Data Support the Use of Momelotinib in Myelofibrosis

Treatment of myelofibrosis (MF) with momelotinib as a first- or second-line therapy outside of a clinical trial yielded significant improvements in anemia and survival rates. Adverse events (AEs) in the studied real-world population were consistent with clinical trial data.

Momelotinib is a Janus kinase (JAK) 1/2 inhibitor that also blocks the action of activin receptor–like kinase 2, reducing hepcidin production, which is involved in MF anemia development. Although momelotinib has been studied in clinical trial settings, its safety and efficacy have not been evaluated in a real-world population. Alexandros Rampotas, MD, PhD, University College London, London, UK, investigated the efficacy of momelotinib in a real-world population in a retrospective study of 119 patients with MF not participating in clinical trials across 20 hospitals throughout the UK.¹

In this real-world population, 60% of patients had additional mutations, had received prior JAK inhibitor treatments, were considered intermediate or high risk, or were transfusion dependent. Their median hemoglobin level at baseline was 87 g/L.

A hemoglobin increase of more than 20 g/L was observed in 48.5% of the participants at 3 months (P<.0001) and 61.3% (P<.0001) at 6 months. The survival rate was 92.9% (95% CI, 85.6-96.5) at 6 months and 85.4% (95% CI, 74-92.1) after one year. Spleen volume reduction was observed in 35.4% of 31 evaluable participants at 3 months. Similarly, total symptom score reduction (TSS) of more than 50% was observed in 36.9% of 46 participants with available TSS.

Although 75% of the participants tolerated momelotinib well, approximately 10% discontinued treatment because of toxicity, and 8.4%, because of disease progression; 12 participants died. The most common adverse events were peripheral neuropathies (13.4%), followed by gastrointestinal symptoms (11.7%); and 18% of participants developed thrombocytosis at 3 months. These data are consistent with clinical trial data; however, rates of thrombocytosis were slightly higher than those in clinical trials.

These real-world findings highlight momelotinib as an effective and practical treatment for managing MF in everyday clinical settings.

Reference

1. Rampotas A, Torre E, Carter-Brzezinski L, et al. Real world efficacy and safety of momelotinib for myelofibrosis: evaluation of a UK-wide study confirms 40% anaemia response rate in a non-clinical trial cohort. Abstract #1804. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.