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.