ODYSSEY phase II preliminary results: Momelotinib + luspatercept in TD MF

Preliminary results from the phase II ODYSSEY trial (NCT06517875), investigating the efficacy and safety of momelotinib + luspatercept in patients with transfusion-dependent (TD) myelofibrosis (MF) with (n = 15) or without (n = 12) prior Janus kinase inhibitor (JAKi) exposure, were presented by Prithviraj Bose at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, December 6–9 2025, Orlando, US. The primary endpoint was transfusion-independent response by Week 24.  As no patients had reached Week 24 at the time of the preliminary analysis, early changes in transfusion burden and spleen length, as well as early safety data, were reported.

Key data: After a median follow-up of 43 days, transfusion burden was stable or reduced in 64% of evaluable patients (n = 7/11) compared with baseline. Additionally, 43% of evaluable patients (n = 6/14) had a reduction in palpable spleen length from baseline, with only one patient experiencing an increase. Adverse events (AEs) were reported in 63% of patients, with no AE-related drug discontinuations. Anemia and thrombocytopenia were the most common AEs (any grade, 19% and 11%, respectively).

Key learning: Preliminary evidence of anemia- and spleen-related benefits with momelotinib + luspatercept was observed, supporting the continued evaluation of this combination in patients with TD MF.