Management of myelofibrosis after ruxolitinib failure

Abstract

Over the last decade, the Janus kinase1/2 (JAK1/2) inhibitor ruxolitinib has emerged as a cornerstone of myelofibrosis (MF) management. Ruxolitinib improves splenomegaly and symptoms regardless of driver mutation status, and confers a survival advantage in patients with intermediate-2/high risk MF. However, cytopenias remain problematic, and evidence for a robust anti-clonal effect is lacking. Furthermore, the median duration of spleen response to ruxolitinib in clinical trials is approximately 3 years, and ruxolitinib does not appear to affect the risk of leukemic transformation. There is no therapy approved specifically for patients whose disease ‘progresses’ on ruxolitinib, defining which remains challenging. The recent regulatory approval of the JAK2 inihibitor fedratinib partially fulfills this unmet need, but much remains to be done. Other JAK inhibitors and a plethora of novel agents are being studied in the ruxolitinib ‘failure’ setting, as well as ‘add-on’ therapies to ruxolitinib in patients having a ‘sub-optimal’ response.

Keywords:

• Myelofibrosis
• ruxolitinib failure
• fedratinib
• momelotinib
• clinical trials
• rational combinations

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The present research was financially supported by National Cancer Institute.