Emerging Treatment Paradigms: Rusfertide’s VERIFY Trial and Molecular Response-Guided Therapy in Advanced PV

This segment explores rusfertide, a novel therapy for polycythemia vera (PV) published in the New England Journal of Medicine in 2024. Dr Rampal explains that rusfertide can eliminate the need for phlebotomies, which is significant as phlebotomies cause iron deficiency with associated symptoms that can be intolerable for some patients. He addresses the “magical thinking” problem in PV management—patients with high hematocrit at 3-month checks were likely at elevated thrombosis risk for much of the intervening period. Maintaining steady hematocrit control with cytoreductive agents or rusfertide could better mitigate this risk.

Dr. Vachhani elaborates that rusfertide is a peptide hepcidin agonist that alters iron homeostasis, reducing phlebotomy requirements. Phase 1/2 studies showed symptom improvements, and preliminary phase 3 data indicates fatigue score improvements and other positive patient-reported outcomes. For monitoring PV patients, Dr Rampal emphasizes tracking phlebotomy frequency, symptom burden, and blood counts (white cells and platelets) that increase thrombosis risk.

Regarding JAK2 allele burden monitoring, Dr. Rampal checks this annually but acknowledges uncertainty about clinical implications. While decreasing allele burden appears positive, it’s unclear whether therapy should be changed to promote this effect. Dr. Vachhani agrees with the annual monitoring approach but similarly questions how to act on the results in clinical practice, highlighting an area where more research is needed to guide therapeutic decisions in PV management.