Ropeginterferon for High Risk JAK2 Clonal Hematopoiesis

Myeloproliferative neoplasms (MPNs) are driven by dysregulation of the JAK/STAT signaling pathway, most commonly due to the JAK2 V617F mutation. Recent data suggest that JAK2 mutations can arise decades before overt disease, representing an early "precursor" state known as JAK2 clonal hematopoiesis. Individuals with JAK2 clonal hematopoiesis have increased risks of both thrombosis and future MPN development. Early intervention to reduce the malignant clone may therefore improve long-term outcomes. This is a prospective cohort feasibility study evaluating ropeginterferon alfa-2b in patients with JAK2 V617F clonal hematopoiesis and high-risk features for thrombosis or progression. Participants will receive ropeginterferon by subcutaneous injection every 4 weeks for up to 2 years. The primary objective is to assess feasibility (enrollment of 12 patients within 2 years) and evaluate the safety and tolerability of ropeginterferon. Secondary objectives include assessing molecular response rates of thrombosis, bleeding, quality of life, and progression to myeloproliferative neoplasm (MPN). every 6 months through year 2, and again at years 3 and 4 to evaluate durability of response.