RUSFERTIDE: A NOVEL THERAPEUTIC STRATEGY FOR CONTROLLING POLYCYTHEMIA VERA AND REDUCING DEPENDENCE ON PHLEBOTOMY

Abstract

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm—associated with the JAK2 V617F mutation in over 95% of cases—characterized by persistent erythrocytosis and an increased risk of thrombotic events. Standard treatment relies on therapeutic phlebotomy, with or without cytoreduction, to maintain hematocrit levels below 45%; however, this approach is limited by the induction or worsening of iron deficiency, incomplete hematologic control between sessions, and a negative impact on quality of life. Rusfertide is a mimetic peptide of hepcidin—the central regulatory hormone of iron metabolism—that acts by blocking ferroportin and restricting iron availability for erythropoiesis, effectively functioning as a "chemical phlebotomy." This study is a literature review aimed at analyzing available scientific evidence regarding the use of rusfertide as a therapeutic strategy for controlling PV and reducing phlebotomy dependence. Five scientific articles indexed in PubMed were selected, covering the pivotal Phase 2 clinical trial (REVIVE), studies on iron pathophysiology in PV, and reviews concerning the hepcidin-ferroportin axis and the limitations of phlebotomy as a standalone therapy. The results demonstrate that rusfertide promotes superior hematologic control compared to placebo, a significant and sustained reduction in phlebotomy frequency, and an improvement in disease-related symptoms, all with a favorable safety profile. However, there is currently no definitive evidence that this hematologic control translates into a reduction of thrombotic events or a modification of the disease's natural history, underscoring the need for Phase 3 trials and long-term follow-up. In conclusion, rusfertide represents a significant advancement in the therapeutic arsenal for PV, particularly for patients dependent on phlebotomy, although its actual impact on hard clinical outcomes remains under investigation.