A comprehensive review of pacritinib in myelofibrosis

Abstract

The first-in-class JAK1/JAK2 inhibitor ruxolitinib inhibits JAK/STAT signaling, inducing durable reductions in splenomegaly and constitutional symptoms in patients with myelofibrosis. However, the association of ruxolitinib therapy with myelosuppression indicates the continued need for optimal treatment choices in myelofibrosis. Pacritinib, a dual JAK2 and FLT3 inhibitor, improves disease-related symptoms and signs with manageable gastrointestinal toxicity in patients with myelofibrosis with splenomegaly and high-risk features, without causing overt myelosuppression, and therefore may provide an important treatment option for a range of patients with myelofibrosis. This article examines the role of JAK2 and FLT3 signaling in myelofibrosis and provides an overview of the clinical development of pacritinib as a new therapy for myelofibrosis.