Pegylated interferon: the who, why, and how

Interferon alpha (IFN-α) is a fascinating molecule with many biological properties yet to be fully understood. Among these properties, several have demonstrated usefulness for targeting malignant cells, including hematopoietic cells from patients with myeloproliferative neoplasms. Indeed, IFN-α has been used for decades across all myeloproliferative neoplasms, but only recently a new form, ropegIFN-α2b, was approved to treat patients with polycythemia vera. Many phase 2 and more recently phase 3 studies have demonstrated IFN-α's promise in treating patients with essential thrombocythemia and early-stage myelofibrosis. In addition, although not approved in that situation, IFN-α is the only cytoreductive therapy that can be used during pregnancy. Today, IFN-α is a key medicine for polycythemia vera and essential thrombocythemia, while its place in the management of myelofibrosis must be better defined. The advantages of IFN therapy include a well-known safety profile, high rates of clinical and molecular responses, and a unique ability to deeply reduce the mutant allele burden of most of the driver mutations causing myeloproliferative neoplasms. Recent preliminary data from prospective studies suggest that molecular responses may be correlated with prolonged event-free survival, raising the hope that IFN therapy may ultimately alter the natural history of many diseases.