Emerging therapies for the treatment of chronic Philadelphia chromosome-negative myeloproliferative neoplasm-associated myelofibrosis

Expert Opin Investig Drugs. 2013 Dec;22(12):1603-11. doi: 10.1517/13543784.2013.832199. Epub 2013 Sep 25.


Introduction: Chronic Philadelphia chromosome-negative myeloproliferative neoplasm-associated myelofibrosis significantly impacts afflicted patients with cytopenia, splenomegaly, debilitating constitutional symptoms and decreased survival. Approval of the first Janus kinase 2 (JAK2) inhibitor therapy, ruxolitinib, has improved splenomegaly, symptomatic burden, survival and perhaps fibrosis in some treated patients; however, other patients remain symptomatic and are in need of alternate therapeutic strategies.

Areas covered: A review of recent literature via PubMed and meeting abstracts has revealed many studies investigating new treatment approaches for chronic Philadelphia chromosome-negative myeloproliferative neoplasms. Multiple additional JAK2 inhibitors (fedratinib, pacritinib and momelotinib) are well into single agent development, as well as multiple combination approaches with ruxolitinib. Efforts to combine JAK2 inhibition with agents to improve cytopenia, marrow fibrosis, additional pathway inhibitors and even allogeneic transplant are planned or ongoing. Additionally, Phase III trials of immunomodulation with pomalidomide are ongoing.

Expert opinion: This article discusses investigational therapies for the treatment of Philadelphia chromosome-negative myeloproliferative neoplasms, particularly those in Phase II clinical trials, employing new JAK2 inhibitors, novel multi-agent therapeutic approaches and innovative new drug targets. Additionally, the future era of Philadelphia chromosome-negative myeloproliferative neoplasms is addressed with potentially expanded niches for JAK2 inhibition.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Myeloproliferative Disorders / drug therapy*
  • Philadelphia Chromosome