Treatment and management of myelofibrosis in the era of JAK inhibitors

Abstract

Myelofibrosis (MF) can present as a primary disorder or evolve from polycythemia vera (PV) or essential thrombocythemia (ET) to post-PV MF or post-ET MF, respectively. MF is characterized by bone marrow fibrosis, splenomegaly, leukoerythroblastosis, extramedullary hematopoiesis, and a collection of debilitating symptoms. Until recently, the therapeutic options for patients with MF consisted of allogeneic hematopoietic stem cell transplant (alloHSCT), the use of cytoreductive agents (ie, hydroxyurea), splenectomy and splenic irradiation for treatment of splenomegaly, and management of anemia with transfusions, erythropoiesis-stimulating agents (ESAs), androgens, and immunomodulatory agents. However, with increased understanding of the pathogenesis of MF resulting from dysregulated Janus kinase (JAK) signaling, new targeted JAK inhibitor therapies, such as ruxolitinib, are now available. The purpose of this article is to review the clinical features of MF, discuss the use and future of JAK inhibitors, reassess when and how to use conventional MF treatments in the context of JAK inhibitors, and provide a perspective on the future of MF treatment.

Keywords: JAK inhibitor; myelofibrosis; ruxolitinib.

Figure 1

Kaplan–Meier analysis of overall survival in (A) COMFORT-I and (B) COMFORT-II with 24 months of follow-up. Note: ^aP-values and CIs are unadjusted for repeat analyses. Republished with permission of American Society of Hematology; High Wire Press, from A comprehensive review and analysis of the effect of ruxolitinib therapy on the survival of patients with myelofibrosis. Mascarenhas J, Hoffman R. Blood. 121(24):2013; permission conveyed through Copyright Clearance Center, Inc. Abbreviations: CI, confidence interval; HR, hazard ratio; BAT, best available therapy; COMFORT, COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment.