Expert perspectives in the management of myelofibrosis (MF): A survey of 20 US-based specialists.

Abstract

e18590 Background: Management of MF has faced a wide variety of clinical challenges. Allogeneic stem cell transplantation (allo-SCT), the only potentially curative therapy, carries substantial treatment burden, limiting its use in many patients with MF. For management without curative intent, conventional strategies often provide modest benefit and are often limited by cytopenias. The introduction of newer JAK inhibitors (JAKi) has broadened options and improved symptom burden and splenomegaly in patients with anemia or thrombocytopenia. With four FDA-approved JAKi now available, this survey examined how MF specialists approach prognostication, monitoring, and treatment to understand how advancements are shaping expert practice patterns amid increasingly complex decision-making. Methods: A cohort of 20 MF specialists from diverse US centers of excellence were invited via email to complete a 34-item survey in September 2025. Data were aggregated and analyzed to inform the development of a CME activity. Respondents were compensated for participating. Results: Most respondents (60%) reported routinely combining molecular (e.g., MIPSS70+ 2.0) and dynamic clinical scoring systems (e.g., DIPSS+) to guide prognosis. Regarding disease monitoring, experts favor a targeted approach: 50% repeat next-generation sequencing (NGS) selectively based on clinical scenario (e.g., transplant candidates) while 40% perform NGS only at disease progression or therapy change. Allo-SCT remains limited, with the majority (60%) pursuing transplant in fewer than 20% of their patients with MF. For INT-1 risk disease, symptom burden emerged as the predominant trigger for treatment initiation (55%), followed by progressive splenomegaly (30%). In the absence of cytopenias, ruxolitinib was overwhelmingly favored (95%) in a patient with INT-2 MF; however, treatment selection was highly cytopenia-dependent: in patients with symptomatic anemia, 85% selected up-front momelotinib. For thrombocytopenic patients with disease progression, 85% switched to pacritinib over other JAKi options. Upon JAKi progression with new-onset cytopenias (Hgb = 7.6 g/dL; platelets = 55,000/µL), 55% switched to momelotinib and 25% to pacritinib. Worsening cytopenias were the leading cause of JAKi discontinuation (70%). Regarding supportive care, ESAs (100%) and luspatercept (85%) were most frequently combined with JAKis to manage anemia, while danazol was used by 40% of respondents. Constitutional symptoms drove therapy switches in ~50% of cases, with 40% reporting that symptoms frequently influenced clinical decisions even in the absence of splenic progression. Conclusions: These findings demonstrate convergence among MF experts in integrated risk stratification and targeted JAKi selection, while underscoring that cytopenias and symptom burden remain key drivers of individualized treatment decisions in current practice.