Effi cacy of primary myelofi brosis therapy with JAK2 inhibitors

Abstract

Primary myelofi brosis (PMF) is a Philadelphia (Ph) negative myeloproliferative neoplasm (MPN)characterized by symptoms derived from anemia and splenomegaly and constitutional symptomsand associated with a median survival of 5–7 years. The effi cacy of current conventional therapy of PMF is modest, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is complicatedby relatively high treatment-related mortality and morbidity. The discovery of molecular mechanisms and role of JAK-STAT pathway dysregulation involved in the pathogenesis of MPN triggered the development of novel, targeted therapies. In this publication the results of PMF therapy with ruxolitinib, CYT378 and SAR302503 — three JAK2 inhibitors documented in phase-I, II and III trials are reported. By the incorporation of JAK2 inhibitors into current PMF therapy a profound symptomatic relief, and hopefully a certain improvement of treatment efficacy and survival prolongation can be achieved.