Pacritinib to treat myelofibrosis patients with thrombocytopenia.

INTRODUCTION: Treatment with ruxolitinib, a selective JAK1/2 inhibitor, has significantly improved the lives of patients with myelofibrosis. Unfortunately, this treatment is frequently limited by cytopenias, precluding a high-risk group characterized by baseline thrombocytopenia. Additionally, there are no approved treatments for patients who have progressed while receiving ruxolitinib. Pacritinib is a novel JAK2/FLT3 inhibitor associated with less treatment-related myelosuppression that has the potential to fill these unmet treatment needs. Areas covered: This review will describe the preclinical rationale for JAK2/FLT3 inhibition, review the pharmacology of pacritinib, and detail available clinical data for pacritinib treatment of myelofibrosis. The circumstances surrounding the full clinical hold temporarily placed on pacritinib will also be explored. Expert commentary: Pacritinib has demonstrated promising results in patients with myelofibrosis and thrombocytopenia. Improvements in splenomegaly and symptom burden were observed with the 200 mg twice-daily dose in PERSIST-2, including those with platelet counts <50,000 mm. Safety concerns pertaining to cardiovascular events and bleeding that arose in an early analysis of PERSIST-2 were likely related to the advanced disease state enrolled rather than clear attribution to pacritinib. The results of an ongoing dose-finding, phase II study are eagerly awaited in order to move this promising myelofibrosis therapy forward.