Myelofibrosis (MF) is a myeloid disorder caused by a clonal hematopoietic stem-cell proliferation associated with activation of the
Janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathways. Patients with MF often develop severe
splenomegaly, marked symptom burden and significant
cytopenias, with a consequent marked negative impact on quality of life and survival. The management of MF patients has dramatically improved with the development of a group of drugs that inhibit JAK signaling. The first of these agents to be approved was
ruxolitinib, a JAK1/JAK2 inhibitor, which has been shown to improve both spleen size and symptoms in patients with MF. However, myelotoxicity, particularly of the platelet lineage, significantly limits the patient population who can benefit from this agent. Thus, there is an unmet need for novel agents with limited myelotoxicity to treat MF.
Pacritinib, a JAK2 and
FMS-like tyrosine kinase 3 (FLT3) inhibitor, has shown promising results in early phase trials with limited myelotoxicity and clinical responses that are comparable with those seen with
ruxolitinib, even in patients with severe
thrombocytopenia. Currently there are two large phase III clinical trials of
pacritinib in MF, including patients with
thrombocytopenia, and those previously treated with
ruxolitinib. If the encouraging results observed in early phase clinical trials are confirmed,
pacritinib will represent a new and exciting treatment option for patients with MF and particularly patients with significant
cytopenias.