Odyssey: Will Adding Luspatercept to Momelotinib Reduce Transfusion Dependence in Patients With MF and Anemia?

The Odyssey study will evaluate the combination of momelotinib and luspatercept in patients with transfusion-dependent myelofibrosis (MF), aiming to improve anemia outcomes. The trial will assess the treatment’s impact on transfusion independence, safety, and efficacy.

MF often results in severe anemia and dependence on blood transfusions, which can poorly affect patients’ quality of life. Patients with MF and anemia frequently have worse prognoses and symptoms than those without it. Momelotinib, a Janus kinase (JAK) 1/2 and activin A receptor 1 (ACVR1) inhibitor, is currently approved for treatment of patients with MF and anemia. Although momelotonib has reduced anemia and anemia-related symptoms for many patients, the investigators hypothesize that adding luspatercept, an erythroid maturation agent, will increase the number of patients with anemia-related benefits.

Odyssey (NCT06517875) is an ongoing, open-label, phase 2 study that will assess the benefit of adding luspatercept to momelotinib treatment in patients with transfusion-dependent MF. This study will consist of two cohorts: a JAK inhibitor–naive group (n=28) and a cohort that has previously received JAK inhibitors (n=28). Both cohorts will receive 200 mg of momelotinib daily, with 1 mg/kg luspatercept every 3 weeks. Patients will be transfusion dependent, meaning they require more than four transfusions of red blood cells or have a hemoglobin level less than 8 g/dL 8 weeks before receiving treatment.

The primary endpoint is transfusion independence, defined as no red blood cell transfusions from week 12 through week 24. Secondary endpoints include safety and tolerability, plasma concentrations of momelotinib and M21 (its major metabolite), and hemoglobin levels.

This study will illuminate whether treating anemia can lead to transfusion independence and whether luspatercept provides additional benefits for patients with anemia and MF than momelotinib alone. Odyssey will begin enrolling patients in early 2025.

Reference

1. Bose P, Gerds AT, Gupta V, et al. Odyssey: a phase 2 open-label study of momelotinib in combination with luspatercept in patients with transfusion-dependent myelofibrosis. Abstract #3191.2. Presented at the American Society of Hematology Annual Meeting; December 7-10, 2024; San Diego, California.