Does ruxolitinib improve survival of persons with MPN-associated myelofibrosis? Should it?

JAK2-activating mutations are linked to development of myeloproliferative neoplasms (MPNs), a discovery that revolutionized the therapy of persons with MPN-associated myelofibrosis. Targeting the JAK/STAT pathway with ruxolitinib, a JAK1/JAK2 inhibitor, suppresses heamatopoiesis and pro-inflammatory cytokines, reduces splenomegaly and disease-related symptoms.1, 2, 3, 4 These effects are not specific for the neoplastic clone and the response rates are similar in persons with and without the JAK2V617F and other JAK2 mutations.5 Based on these data, ruxolitinib was approved by the US Food and Drug Administration (FDA) for therapy of splenomegaly in persons with >intermediate-risk MPN-associated myelofibrosis (staging system unspecified), and by the European Medicines Agency (EMA) for therapy of splenomegaly and/or symptoms in persons with MPN-associated myelofibrosis for all disease stages.