Emerging drugs for the treatment of myelofibrosis

Expert Opin Emerg Drugs. 2015;20(4):663-78. doi: 10.1517/14728214.2015.1061502. Epub 2015 Jul 8.


Introduction: Myelofibrosis (MF) is a myeloproliferative neoplasm associated with significant disease burden composed of splenomegaly, constitutional symptoms and a reduced life expectancy. The advent of targeted treatments has provided new means by which to improve MF associated splenomegaly, symptoms, health-related quality of life and even mortality.

Areas covered: We discuss the spectrum of targeted treatments currently under investigation for MF. We furthermore compare their effects on improving anemia, reducing fibrosis and splenomegaly and enhancing symptom control.

Expert opinion: MF is a complex disorder, partly attributable to its heterogeneity. Although the severity of patient symptoms correlates with risk category, high symptom burden may also be observed in low-risk patients. Serial use of PRO tools allows clinicians to objectively evaluate the MF symptom burden, compare efficacy of therapies and adjust medications to improve symptom control. Novel targeted agents have proven superior to historic treatment regimens for symptom management. Promising treatment categories include JAK2 inhibitors, histone deacetylase inhibitors, hypomethylating agents, heat shock protein-90 inhibitors, hedgehog inhibitors, PI3-AKT-mTOR inhibitors, antifibrosing agents and telomerase inhibitors. The majority of therapies remain under investigation, either alone or in combination with other treatments. It is anticipated that these agents will be increasingly integrated into standard treatment algorithms for MF symptom management.

Keywords: HDAC inhibitors; HSP90 inhibitors; JAK2 inhibitor; PI3-AKT-mTOR inhibitors; antifibrosing agents; hedgehog inhibitors; hypomethylating agents; myelofibrosis; myeloproliferative neoplasms; quality of life; symptoms; targeted therapy, telomerase inhibitors.

Publication types

  • Review

MeSH terms

  • Algorithms
  • Animals
  • Drug Design*
  • Humans
  • Life Expectancy
  • Molecular Targeted Therapy
  • Primary Myelofibrosis / drug therapy*
  • Primary Myelofibrosis / physiopathology
  • Quality of Life*
  • Severity of Illness Index
  • Splenomegaly / etiology