A paradigm shift in the treatment of patients with polycythemia vera. The initial early use of recombinant...

During the past 35 years, single-arm studies documented the efficacy and safety of recombinant interferon alpha (rIFNα) for treating polycythemia vera (PV). In some patients, 2-5 years of disease-modifying treatment resulted in symptom relief, regression of splenomegaly, normalization of abnormal blood counts and marrow morphology, and sustained JAK2V617F molecular remission. The PROUD-CONTI study showed the superiority of rIFNα compared to hydroxyurea (HU), which led to the European Medicines Agency approval in 2019 of ropeginterferon alpha-2b ("ropegIFN") for ELN-defined high-risk PV patients. In 2021, the Food and Drug Administration (USA) gave unrestricted approval, except for pregnant PV patients. The Low-PV randomized trial established the superiority of ropegIFN compared to phlebotomy-only (PHLEB-O) in ELN-defined low-risk patients. Nevertheless, worldwide, HU remains the cytoreductive drug most often used; maintenance PHLEB-O is still endorsed as maintenance therapy by some hematologists. The National Comprehensive Cancer Network (NCCN, USA) approved ropegIFN as a II-A recommendation for ELN-defined low and high-risk disease; the ELN suggested criteria for using rIFNα in low-risk patients if certain issues developed after PHLEB-O, including more symptoms, progressive splenomegaly, significant leukocytosis, thrombocytosis, or inadequate hematocrit control. These issues are important because even low-risk patients are at increased thrombotic risk, estimated at 2 to 3 times that of the general population. Moreover, as PV progresses, the development of myelofibrosis is the leading cause of morbidity, perhaps abetted by PHLEB-O. Here, we review recent progress in the treatment of PV with rIFNα and discuss our rationales and perspectives for, and the endorsement of the initial treatment with rIFNα of both low and high-risk PV patients, unless a contraindication exists to its use.