Momelotinib Shows Real-World Improvements in Anemia, Symptoms, and Spleen Response in Myelofibrosis

Treatment with momelotinib (Ojjaara) improved anemia, and increased rates of transfusion independence (TI) in patients with myelofibrosis; the agent also alleviated symptoms and controlled splenomegaly for those previously exposed to a JAK inhibitor, according to real-world data from a retrospective study presented at the 2024 ASH Annual Meeting.1

Among patients who were symptomatic at baseline (n = 126), 92% experienced improvement in disease-related symptoms, including asthenia (76%), anorexia (65%), weight loss (51%), abdominal discomfort (47%), and pruritis (75%). Improvements were sustained at 3-, 6-, 9- and 12-month assessments.

Moreover, the mean hemoglobin level increased from 8.0 g/dL at baseline to 9.3 g/dL at 3 months and was maintained at 9.2 g/dL at 6 months. At 3 months of follow-up, 48.4% of patients who were transfusion dependent (TD) prior to treatment with momelotinib (n = 108) achieved TI; these rates were 45.7%, 42.9% and 44.4% at 6, 9, and 12 months, respectively. Furthermore, the rate of TI was 49.3% among JAK inhibitor–exposed patients vs 31.6% in JAK inhibitor–naive patients. Among patients who remained TD, the median number of red blood cell (RBC) units per month decreased from 4 to 2.25.

Further analysis of transfusion intensity during the treatment period showed that 50.8% of patients transitioned to a lower category. Conversely, 41.1% remained in the same transfusion intensity category, and 8.1% moved to a higher category.

Of those evaluable for spleen response (n = 45), 62.2% of patients experienced an improvement in spleen size with a median reduction of 5 cm. However, only 24.4% of patients met the European LeukemiaNet (ELN) International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) criteria for spleen response, and these patients had a median reduction of 10 cm). Notably, 26.7% of patients (n = 12) evaluable for spleen response maintained stable splenomegaly without a significant decrease; 3 patients showed refractoriness, and 2 experienced an increase in spleen size.

“Momelotinib significantly improves anemia in patients with myelofibrosis, achieving high rates of TI [that are] more pronounced in JAK inhibitor–exposed than JAK inhibitor–naive patients,” lead study author Lucía Pérez-Lamas, MD, of Ramón y Cajal University Hospital in Madrid, Spain, and colleagues wrote in a poster presentation of the data. “Momelotinib [also] effectively alleviates symptoms and controls splenomegaly in patients previously treated with ruxolitinib [Jakafi], maintaining an acceptable safety profile.”

In September 2024, momelotinib gained FDA approval for the treatment of adult patients with intermediate or high-risk myelofibrosis and anemia, based on data from the phase 3 MOMENTUM trial (NCT04173494) and data for a subpopulation of adult patients with anemia enrolled in the phase 3 SIMPLIFY-1 trial (NCT01969838).2 In both trials, momelotinib produced a significant improvement in anemia and addressed both disease-related symptoms and splenomegaly in patients previously exposed to JAK inhibitors. Momelotinib also improved anemia and transfusion burden as first-line therapy vs ruxolitinib in the phase 3 SIMPLIFY-2 trial (NCT02101268).1 However, data regarding the agent’s real-world benefit were lacking.

Therefore, investigators conducted a multicenter, observational, retrospective study of 154 patients with myelofibrosis who received momelotinib through a managed-access program in Spain from March 2023 to July 2024 across 74 centers.

Both JAK inhibitor–naive and –exposed patients were included in the retrospective study, and patients were also required to have splenomegaly or symptoms and anemia, defined as a hemoglobin value of less than 11 g/dL for men and less than 10 g/dL for women. Anemia assessment was based on revised 2024 IWG-ELN criteria in myelofibrosis, and splenomegaly was assessed according to 2013 ELN IWG-MRT criteria. Patients with a baseline splenomegaly of more than 5 cm below the left costal margin (LCM) were evaluable for spleen response. Response criteria included a baseline splenomegaly palpable at 5 cm to 10 cm below the LCM that becomes not palpable, or baseline splenomegaly palpable at 10 cm below the LCM that decreases by 50%. TD was defined at least 1 RBC unit per month or at least 3 units in the past 12 weeks.

Patients with follow-up of more than 1 month were considered efficacy evaluable; all patients who received the agent at any dose level were included in the safety analysis.

The median age was 73 years (interquartile range [IQR], ±10.7) at the start of treatment with momelotinib, and most patients were male (61.7%). Primary myelofibrosis was the most common subtype (60%) followed by after essential thrombocythemia (29%) and after polycythemia vera (10%); subtype data were not available for 1 patient. The most frequently observed driver mutation was JAK2 (63%), followed by CALR (22.7%), triple-negative (6.5%), MPL (5.8%), and not available (2%). Prior receipt of a JAK inhibitor was reported in 76.6% of patients vs 23.4% who were JAK inhibitor–naive.

The median number of prior lines of therapy was 1 (IQR, ±1). Regarding Dynamic International Prognostic Scoring System risk category, most patients had intermediate-2 (43.5%) or high-risk (42.9%) disease; 3.9% of patients had intermediate-1 disease, and data were not available for 9.7% of patients. Among patients with available cytogenetic data (n = 94), 11.78% had unfavorable-risk cytogenetics, and 5.3% had very high–risk cytogenetics. Data on additional mutations by next-generation sequencing were available in 108 patients; they included ASXL1 (34.3%), SRSF2 (8.3%), EZH2 (8.3%), IDH1/2 (3.7%) and U2AF1 (11.1%).

The baseline median hemoglobin was 8.0 g/dL (range, 4.7-13.5); median platelet count was 16 x 109 μL (range, 3-1812); median leukocyte count was 6.3 x 109 μL (range, 0.5-101). The median number of peripheral blasts was 1 (range, 0-13). TD patients required a median of 3 RBC units per month (range, 1-8)

After a median follow-up of 5.48 months (range, 1-14), 79% of patients continued treatment. Treatment discontinuations were attributed to hematopoietic stem cell transplant (n = 3), lack of efficacy (n = 5), disease progression (PD; n = 2), transformation of disease to acute myeloid leukemia (n = 5), toxicity (n = 6), and death (n = 11). Deaths occurred due to infections (n = 5), severe hemorrhages (n =3), PD (n = 2), and unknown cause (n = 1). Dose reductions were required in 26 patients, and 10 temporarily discontinued treatment, primarily due to infections or cytopenias.

The most common adverse effects (AEs) included diarrhea (any grade, 11.7%; grade 1/2, 9.7%; grade 3/4, 2.1%), thrombocytopenia (10%; 4.1%; 6.2%), infections (9%; 4.8%; 2.8%), nausea (6.2%; 5.5%; 0.7%), hepatotoxicity (5.5%; 2.8%; 2.8%), and dizziness (5.5%; 4.1%; 0.7%). Other AEs observed were peripheral neuropathy (4.8%; 4.1%; 0.7%), anemia (4.2%; 2.1%; 2.1%), abdominal pain (2.8%; 2.8%; 0%), hypotension (2.1% 1.4%; 0.7%), renal impairment (2.1% 1.4%; 0.7%), headache (1.4%; 0.7%; 0.7%), dyspnea (0.7%; 0.7%; 0%), and edema (0.7%; 0.7%; 0%).

References

1. Perez-Lamas L, Diaz AS, Delgado RG, et al. Real-world outcomes of momelotinib as an alternative therapy to other JAK inhibitors in myelofibrosis patients with anemia. Blood. 2024;144(suppl 1):1790. 10.1182/blood-2024-200698
2. Ojaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia. News release. GlaxoSmithKline. September 15, 2023. Accessed December 9, 2024. https://www.gsk.com/en-gb/media/press-releases/ojjaara-momelotinib-approved-in-the-us-as-the-first-and-only-treatment-indicated-for-myelofibrosis-patients-with-anaemia