Advances in the therapy of primary myelofibrosis

Abstract

Primary myelofibrosis (PMF) harbors the worst prognosis among the Philadelphia chromosome-negative chronic myeloproliferative neoplasms. The most important clinical issues in thecourse of this disorder are: progressive fibrosis of the bone marrow, splenomegaly and systemicsymptoms. The current clinical management has limited efficacy and is largely palliative.Allogeneic hematopoietic stem cell transplantation is currently the only therapeutic approachpotentially curative, but it is complicated by relatively high treatment-related mortality andmorbidity. Among other drugs that are currently in clinical trials for PMF, pomalidomide andthree JAK-2 inhibitors (CYT387, TG101348 and INCB018424) appear to be the most promisingcompounds due to their effectiveness suggested by the preliminary results. Introduction ofJAK-2 inhibitors for management of PMF resultes in the significant improvement in reductionof splenomegaly and systemic symptoms and, moreover, may further improve the outcomeof patients with PMF.