New drugs for myelofibrosis

ABSTRACT

Introduction: Myelofibrosis (MF) is a clonal myeloid neoplasm associated with cytopenias, significant symptom burden and risk of transformation to acute leukemia. Discovery of the JAK2V617F mutation in the majority of patients with myeloproliferative neoplasms led to the development and approval of ruxolitinib, the first JAK1/2 inhibitor for use in clinical practice. Better understanding of the molecular biology of MF has led to the development of a variety of new drugs that are currently undergoing testing for MF.

Areas covered: Here we discuss the diagnosis and risk stratification of patients with MF. We review the use of ruxolitinib, ongoing studies in combination with this agent, and examine the spectrum of therapies under investigation for MF.

Expert opinion: Ruxolitinib represents an important step in the treatment of MF; it can effectively alleviate symptomatic burden and reduce splenomegaly, unfortunately it does not lead to disease remissions. As a result, several new JAK inhibitors are undergoing advanced clinical testing, notably momelotinib and pacritinib. In addition, several trials are focusing on combinations with these agents. Improved understanding of the disease biology of MF has encouraged the development of new agents with a variety of targets, such as fibrosis, telomerase, PI3K, hedgehog, HSP90 and mTOR inhibition among others.

KEYWORDS:

• Myeloproliferative neoplasm
• myelofibrosis
• JAK inhibitor
• targeted therapy

Article highlights

• Discuss the diagnostic criteria and risk stratification models for patients with MF.

• Review treatment algorithms for patients with MF using approved agents.

• Discuss the use and limitations of ruxolitinib.

• In-depth review of agents under development for the treatment of MF.

This box summarizes key points contained in the article.

Declaration of interest

R Mesa has received research support from NS Pharma, Incyte, Gilead, CTI, Promedior and Genentech, and has participated as a consultant for Novartis. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.