Assessing efficacy in myelofibrosis treatment: a focus on JAK inhibition

Abstract

Myelofibrosis (MF) is characterized by splenomegaly, anemia and a debilitating symptom burden (e.g., fatigue, night sweats, pruritus, bone and muscle pain, undesired weight loss). Moreover, these symptoms impair activities of daily living and quality of life. Until recently, there have been no approved therapies for MF, and management of MF has been predominantly palliative. Dysregulated JAK-STAT signaling is associated with the pathologic MF disease state. A novel class of therapies, the JAK inhibitors, offers the potential to abrogate this pathologic signaling pathway. In clinical trials of patients with intermediate- and high-risk MF, JAK inhibitors have demonstrated efficacy in reducing splenomegaly and MF-associated symptoms. Evidence from ruxolitinib trials also suggests that JAK inhibitors may improve survival outcomes.

Keywords::

• CYT387
• JAK
• JAK-STAT
• Janus kinase
• LY2784544
• myelofibrosis
• pacritinib
• quality of life
• ruxolitinib
• SAR302503

Acknowledgements

We would like to thank Nicholas J Sarlis (Incyte Corp.) for helpful scientific exchange and thoughtful discussions on recent clinical study data.

Financial & competing interests disclosure

Srdan Verstovsek has disclosed the following relevant financial relationships: grant support from Incyte Corp., Lilly Oncology, Bristol-Meyers, AstraZeneca, Geron Corp., YM Biosciences, Celgene, Gilead, Roche, Infinity Pharmaceuticals, S*BIO, NS Pharma and Exelixis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Editorial support was provided by Susan Kralian of The Curry Rockefeller Group and funded by Incyte Corp.