Among real-world patients with myelofibrosis in the ERNEST-3 registry, cytopenic MF subtypes were common at diagnosis, impacted treatment decisions, and were associated with poorer outcomes compared with proliferative MF, according to a presentation at the 2026 European Hematology Association Congress in Stockholm, Sweden.
Furthermore, patients with proliferative MF at diagnosis often converted into cytopenic MF, while patients with cytopenic MF at diagnosis often worsened over time, reported lead author Tiziano Barbui, MD, of FROM Research Foundation at Bergamo Hospital.
The analysis included 418 patients diagnosed with MF between January 2018 and January 2026 at 21 European centers. At time of diagnosis, 232 patients (55%) had proliferative MF and 186 (45%) had cytopenic MF, including 115 with moderate anemia, 41 with severe anemia, and 30 with leukopenia, thrombocytopenia, or combined cytopenias.
The majority of patients with proliferative MF were treated with either ruxolitinib (56%) or hydroxyurea (43%). Patients with cytopenic MF were treated with ruxolitinib (55%), hydroxyurea (33%), fedratinib (11%), momelotinib (11%), interferon therapy (1%), and pacritinib (1%). The limited use of momelotinib was likely due to its recent approval rather than limited selection, the authors wrote.
Compared with proliferative MF, cytopenic MF was associated with more splenomegaly (73% vs 66%), more higher-grade marrow fibrosis (41% vs 21%), more additional myeloid mutations (69% vs 56%), lower JAK2V617F allele burden (38% vs 60%), and fewer CALR mutations (17% vs 25%). In addition, 43% of patients with cytopenic MF versus 19% of patients with proliferative MF had thrombosis, bleeding, disease progression, second cancers, transplantation, or death (P<.001). Three-year event-free survival was 52% for cytopenic MF compared with 83% for proliferative MF.
Among patients with proliferative MF at diagnosis, 48% transitioned to cytopenic MF subgroups, including 30% to moderate anemia, 10% to severe anemia, and 8% to combined cytopenias. Among patients with moderate anemia at diagnosis, 21% transitioned to proliferative MF, 42% had no change, and 35% and 3% progressed to severe anemia or other cytopenias, respectively. Among patients with severe anemia at diagnosis, 56% had no change, 17% improved to moderate anemia, and 27% transitioned to proliferative MF. Among patients with other cytopenias, 30% had no change, 33% shifted to moderate anemia, 10% shifted to severe anemia, and 27% transitioned to proliferative MF.
“Expanding ERNEST-3 and newer JAK inhibitors will enable treatment-specific analyses, including real-world momelotinib anemia improvement,” Dr. Barbui and colleagues wrote.
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