New drugs for myelofibrosis

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.