A closer look at pacritinib: a JAK2/FLT3 inhibitor for the treatment of myelofibrosis

Abstract

Introduction: Myelofibrosis (MF) is a chronic myeloid neoplasm that bears a significant symptom burden, impacts on quality of life and carries a risk of transformation to acute leukemia. Advances in MF therapy by inhibition of Janus kinase type 2 (JAK2) receptor have shown clinical improvements in spleen size and symptom burden, but are often limited by hematological side effects.

Areas covered: Treatment for patients with MF who are not suitable candidates for allogeneic stem cell transplant is limited and, historically, palliative in intent. The approval of ruxolitinib, a JAK2 inhibitor, has enabled clinical improvement in these individuals. In this paper, treatments for MF are briefly reviewed, including historically palliative therapies and the clinical data leading to ruxolitinib approval. This JAK2 therapy is limited by cytopenias, either due to the disease process or a medication side effect. Finally, the preclinical and clinical data of pacritinib use in MF and other hematologic conditions are evaluated.

Expert opinion: Ruxolitinib use in patients with MF who are deemed to be inappropriate transplant candidates can be limited by cytopenias, particularly thrombocytopenia. This demonstrates an unmet therapeutic need in patients with MF. Pacritinib, SB1518, a dual JAK2 and FMS-like tyrosine kinase 3 inhibitor has been suggested to provide clinical benefit to patients with MF without producing adverse hematologic events that restrict ruxolitinib utility. If ongoing phase 3 trials of pacritinib are positive, based on efficacy to improve splenomegaly and constitutional symptoms with a tolerable adverse event profile, pacritinib may provide a much needed oral therapeutic option for patients with MF.

Keywords::

• hematologic malignancy
• Janus kinase type 2 inhibitors
• myelofibrosis
• myeloproliferative neoplasm
• pacritinib
• SB1518