The new landscape of therapy for myelofibrosis

Curr Hematol Malig Rep. 2013 Dec;8(4):325-32. doi: 10.1007/s11899-013-0178-x.


The landscape of therapy for myelofibrosis (MF) is evolving at a pace not previously seen for this clonal myeloproliferative neoplasm. The discovery of the JAK2 V617F mutation in 2005 has led to the rapid development of therapy specifically developed for afflicted MF patients. Indeed, the successful phase III studies of ruxolitinib demonstrating improved symptomatic burden, splenomegaly and survival led to the first approved myelofibrosis drug in the United States and Europe. Multiple additional JAK2 inhibitors are currently in or nearing phase III testing, including SAR302503 (fedratinib), SB1518 (pacritinib) and CYT387 (momelotinib), seeking to offer incremental benefits to ruxolitinib in regards to cytopenias or other disease features. In parallel, phase III testing of pomalidomide is ongoing, with the goal of solidifying the role of immunomodulatory therapy in MF-associated anemia. Multiple single agents strategies are ongoing with histone deacetylase inhibitors, hedgehog inhibitors and hypomethylation agents. Incremental advances are further sought, either in additive or synergistic fashion, from combination strategies of ruxolitinib with multiple different approaches ranging from allogeneic stem cell transplant to current therapies mitigating anemia and further impacting the bone marrow microenvironment or histology. Transitioning from a pre-2011 era devoid of approved MF therapies to one of multiple agents that target not only disease course but symptomatic burden has indeed changed the platform from which MF providers are able to launch individualized treatment plans. In this article, we discuss the diagnostic and therapeutic milestones achieved through MF research and review the emerging pharmacologic agents on the treatment horizon.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Hematologic Neoplasms / drug therapy*
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Immunologic Factors / therapeutic use
  • Janus Kinases / antagonists & inhibitors*
  • Primary Myelofibrosis / drug therapy*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use*


  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • INCB018424
  • Immunologic Factors
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Janus Kinases