The management of polycythemia vera (PV) is undergoing significant transformation with the emergence of novel therapeutic approaches that target key disease mechanisms and improve patient outcomes. Leading experts are particularly excited about advances in hepcidin mimetics and interferon-based treatments that address both symptomatic relief and potential disease modification.
Rusfertide: A Breakthrough in Phlebotomy Reduction
Rusfertide has emerged as a promising solution for patients struggling with frequent phlebotomy requirements. This novel hepcidin mimetic, administered as a weekly subcutaneous injection, works by increasing hepcidin levels and blocking ferroportin, effectively restricting iron availability for red blood cell production. In the phase 2 REVIVE trial, rusfertide demonstrated remarkable efficacy, eliminating phlebotomy needs in 69.2% of participants.
"Phlebotomies are cumbersome," explains Dr. Naseema Gangat, professor of medicine and consultant in hematology at the Mayo Clinic Comprehensive Cancer Center. "If a patient goes into [the clinic] for repeated phlebotomies to keep their hematocrit levels below 45%, they become depleted in iron, which can cause symptoms of iron deficiency."
Advancing Disease-Modifying Approaches
The treatment landscape has been further enhanced by ropeginterferon alfa-2b-njft (Besremi), a long-acting interferon preparation that shows promise in disease modification through JAK2 allelic burden reduction. Similarly, ruxolitinib has demonstrated effectiveness in reducing JAK2 allele levels in the phase 2 MAJIC-PV study, particularly benefiting patients transitioning to myelofibrosis or experiencing significant constitutional symptoms and splenomegaly.
Future Therapeutic Directions
The field of PV treatment continues to evolve, with several new agents under development. These emerging therapies focus on hepcidin modulation with potentially extended dosing intervals of three to six months, representing a significant improvement over current weekly administration schedules.
"PV is an exciting disease [to manage]," notes Dr. Gangat. "The unmet need continues to be [the discovery of a] disease-modifying therapy." While long-term data on disease transformation risks are still pending, the reduction in JAK2 allelic burden observed with interferons suggests promising therapeutic potential.
Treatment Selection Considerations
Rusfertide's role appears particularly valuable for low-risk patients not requiring other chemotherapy agents. However, it specifically targets hematocrit levels without addressing other disease aspects such as elevated white blood cell counts, platelet counts, or splenomegaly. For patients already receiving chemotherapy agents like hydroxyurea or interferon, these treatments may sufficiently manage hemoglobin and hematocrit levels without requiring additional intervention.
