Real-World Baseline Characteristics and Preliminary Outcomes in Patients with Myelofibrosis Treated with Momelotinib in the US Community Oncology Practice Setting

Background: Myelofibrosis (MF) is a rare and progressive hematologic malignancy characterized by key hallmarks, including anemia, thrombocytopenia, splenomegaly, and constitutional symptoms. Anemia, the need for red blood cell transfusions, and thrombocytopenia are associated with negative quality of life and prognostic impacts. JAK inhibitors such as ruxolitinib and fedratinib have shown positive effects on spleen size and symptom burden; however, they do not address and may exacerbate anemia. Alternative approaches to anemia management involving supportive therapies are of limited efficacy.

The JAK1/JAK2/ACVR1 inhibitor momelotinib, which received US regulatory approval in September 2023, is the first and only treatment specifically indicated for patients with intermediate- or high-risk MF and anemia. Momelotinib was associated with anemia-related benefits, including increased mean hemoglobin levels and transfusion independence rates, as well as spleen and symptom improvements across 3 phase 3 trials in both JAK inhibitor–naive and –experienced patients with MF. Given its recent approval, data on early adoption and outcomes with momelotinib in real-world clinical practice are lacking. We report the first real-world study of momelotinib use in patients with MF and anemia in the US community oncology practice setting, evaluating their demographic, clinical, and treatment characteristics.

Methods: This retrospective, observational, cohort study used the US Oncology Network iKnowMed electronic health record (EHR) database. The study included adult patients (≥18 years old) with MF (primary or secondary) who received treatment with momelotinib following an anemia diagnosis between September 15, 2023, and May 31, 2024. Anemia was defined as the first available laboratory result with a hemoglobin level of <10 g/dL. Momelotinib prescription date was defined as the index date, and patients were followed until the earliest of death, last recorded activity, or end of the observation period (May 31, 2024), whichever occurred first. Patients were excluded if they enrolled in a clinical trial or received treatment for another primary cancer after index and before the end of observation. Baseline characteristics, momelotinib dose, and duration of follow-up were sourced from structured fields in the EHR and summarized descriptively; hemoglobin improvement was measured in 3-month intervals, and time to first hemoglobin improvement of ≥1 g/dL was assessed via Kaplan-Meier analysis.

Results: A total of 4019 patients with a diagnosis of MF were identified, of which 1422 were diagnosed with subsequent anemia; 49 received momelotinib and met inclusion criteria, with a median duration of follow-up of 3.7 months (IQR, 1.7-6.5 months). Median age at anemia diagnosis was 72 years (IQR, 66-78 years), 61.2% of patients were female, and 87.8% were JAK inhibitor experienced; median age at MF diagnosis was 70 years (IQR, 64-77 years). Median time from MF diagnosis to first anemia diagnosis was 5.3 months (IQR, 1.1-18.5 months). At anemia diagnosis, 79.6% of patients had moderate anemia (hemoglobin 8 to <10 g/dL), and 20.4% had severe anemia (hemoglobin <8 g/dL). Most patients (83.7%) initiated momelotinib at the full 200-mg daily dose.

The median hemoglobin level at baseline was 8.2 g/dL (IQR, 7.6-9.7 g/dL); at 3 months post index, it had improved to 9.9 g/dL (IQR, 8.2-10.9 g/dL). During the first 8 weeks after being on momelotinib for 4 months, the median hemoglobin level was 10.2 g/dL (IQR, 8.5-11.2 g/dL). 40.8% of patients had hemoglobin improvement of ≥1 g/dL; median time to first improvement was 18.3 weeks (95% CI, 9.9 weeks to not reached). Median platelet counts improved from baseline (194×10⁹/L [IQR, 108-367×10⁹/L]) to 3 months post index (242×10⁹/L [IQR, 97-479×10⁹/L]).

Conclusion: Most patients with MF and anemia in this US community practice setting had prior JAK inhibitor exposure at the time of momelotinib initiation, highlighting the high medical need in this patient population. Early results demonstrated higher hemoglobin levels and platelet counts after 3 months of treatment, suggesting momelotinib may benefit patients with anemia and thrombocytopenia. These findings provide important real-world insight into the ability of momelotinib to address the clinical needs of patients with MF and anemia and highlight its adaptability to the real-world community oncology practice setting.