Journal: Leukemia
This publication is a narrative review on the modern role of recombinant interferon‑alpha, particularly ropeginterferon alfa‑2b (ropegIFN), in the management of polycythemia vera (PV).
Key points:
- Historical data over 35+ years from single-arm studies show rIFNα can provide disease‑modifying benefit in PV, including:
- Symptom improvement and splenomegaly regression
- Normalization of blood counts and bone marrow morphology
- Deep and sometimes sustained molecular remissions with reduction/eradication of JAK2V617F
- The PROUD‑CONTINUATION (PROUD‑CONTI) study demonstrated superiority of ropegIFN over hydroxyurea (HU), leading to:
- European regulatory approval of ropegIFN for high‑risk PV
- Subsequent broad approval in the United States, with the exception of pregnant patients
- The Low‑PV randomized trial showed ropegIFN is superior to phlebotomy‑only in low‑risk PV, challenging the traditional paradigm that low‑risk patients should be managed long term with phlebotomy alone plus aspirin.
- Despite these data, HU remains the most widely used cytoreductive agent worldwide, and maintenance phlebotomy‑only is still practiced and supported by some clinicians.
- Guideline evolution:
- A major U.S. guideline body now lists ropegIFN as a category II‑A option for both low‑ and high‑risk PV.
- European recommendations suggest introducing rIFNα in low‑risk patients who develop increasing symptoms, progressive splenomegaly, significant leukocytosis or thrombocytosis, or inadequate hematocrit control on phlebotomy.
- The review underscores that:
- Even “low‑risk” PV patients have a thrombotic risk about 2–3× that of the general population.
- Progression to myelofibrosis is a major driver of morbidity and may be facilitated by a long‑term phlebotomy‑only strategy.
- The authors synthesize these data to argue for:
- Preferential use of rIFNα, particularly ropegIFN, as initial therapy for both low‑ and high‑risk PV where not contraindicated, aiming for disease modification rather than simple hematocrit control.