Novel and emerging therapies for the treatment of polycythemia vera

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm defined by erythrocytosis and often accompanied by leukocytosis and thrombocytosis. Current treatment options, including IFN-α and hydroxyurea, effectively manage PV in many patients. However, some high-risk patients, particularly those who become hydroxyurea-intolerant/resistant, may benefit from IFN-α or new treatment options. A better understanding of PV pathophysiology, including the role of the JAK/STAT pathway, has inspired the development of new therapies. Several JAK inhibitors directly target JAK/STAT pathway activation and have been evaluated in Phase II/III trials with promising results. Pegylated variants of IFN-α, which reduce dosing frequency and toxicity associated with recombinant IFN-α, have yielded favorable efficacy results in Phase II trials. Finally, histone deacetylase inhibitors have been developed to manage PV at the level of chromatin-regulated gene expression. The earliest Phase III results from these next-generation therapies are expected in 2014.