Mechanism of Action of Ropeginterferon Alfa-2b in Polycythemia Vera Treatment

Janus kinase 2 (JAK2) with the substitution mutation of valine (Val) to phenylalanine (Phe) at codon 617 (JAK2V617F) is suspected to play a critical role and is termed "driver mutation" in the occurrence and progression of polycythemia vera (PV), a Philadelphia chromosome-negative myeloproliferative neoplasm (MPN). 1 Baxter EJ Scott LM Campbell PJ et al. Cancer Genome Project. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005; 365: 1054-1061 Google Scholar –3 Gisslinger H Klade C Georgiev P et al. Event-free survival in patients with polycythemia vera treated with ropeginterferon alfa-2b versus best available treatment. Leukemia. 2023; 37: 2129-2132 Google Scholar JAK2V617F is present in approximately 97% of patients with PV. 1 Baxter EJ Scott LM Campbell PJ et al. Cancer Genome Project. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005; 365: 1054-1061 Google Scholar It is also present in other types of MPNs, including in approximately 57% of patients with essential thrombocythemia (ET) and 50% of patients with primary myelofibrosis (PMF). 1 Baxter EJ Scott LM Campbell PJ et al. Cancer Genome Project. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005; 365: 1054-1061 Google Scholar The molecular response resulting from the reduction of its allelic burden may be associated with patient event-free or progression-free survival, and decreased risk of thrombosis. 2 Harrison CN Nangalia J Boucher R et al. Ruxolitinib versus best available therapy for polycythemia vera intolerant or resistant to hydroxycarbamide in a randomized trial. J Clin Oncol. 2023; 41: 3534-3544 Google Scholar –4 Moliterno AR Kaizer H Reeves BN. JAK2V617F allele burden in polycythemia vera: burden of proof. Blood. 2023; 141: 1934-1942 Google Scholar