Management of myelofibrosis: JAK inhibition and beyond

ABSTRACT

Introduction: Myelofibrosis (MF) is characterized by bone marrow fibrosis with subsequent extramedullary hematopoiesis and abnormal cytokine expression leading to splenomegaly, constitutional symptoms and cytopenias. The discovery of the JAK2 V617F mutation in the majority of MF patients has been followed by significant progress in drug development for MF.

Areas covered: In this article, we review advances in the understanding of the underlying disease biology, prognostic assessment and therapeutic modalities for MF. We provide clinical trial evidence behind using the JAK2 inhibitor ruxolitinib, erythropoiesis stimulating agents, androgens, immunomodulatory drugs, interferon, cytoreductive drugs and hypomethylating agents in MF. Finally, we review novel therapeutic options for MF including the new JAK1/2 inhibitors, ruxolitinib based combination approaches as well as novel therapeutic agents.

Expert commentary: Despite significant reduction of splenomegaly and improvement of symptom burden and a signal for survival improvement, ruxolitinib does not lead to major reductions in JAK2 V617F allele burden and bone marrow fibrosis. No ruxolitinib-based combination approach has so far demonstrated superiority over ruxolitinib monotherapy. The novel JAK2 inhibitors pacritinib and momelotinib, other JAK inhibitors, telomerase inhibitors, anti-fibrosis agents and hsp90 inhibitors are in different stages of development.

KEYWORDS:

• Myelofibrosis
• JAK inhibitor
• ruxolitinib
• pacritinib
• momelotinib and imetelstat

Declaration of interest

A Zeidan served as a consultant for and received honoraria from Ariad, Gilead, Pfizer, Incyte and Celgene. A zeidan also served as a speaker for Ariad. 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.

Additional information

Funding

This manuscript was not funded.