The role of pacritinib in the management of myelofibrosis

Abstract

The recent discovery of the JAK2 mutation and its role in the pathogenesis of myeloproliferative neoplasms led to the development of a novel class of therapeutic agents, the oral JAK2 inhibitors. These agents are effective in decreasing organomegaly and ameliorating constitutional symptoms in patients with myelofibrosis, regardless of the mutational status. Among this new class of agents is pacritinib, a dual JAK2 and FLT3 inhibitor that showed evidence of clinical efficacy in early-phase trials of patients with myelofibrosis, with limited hematologic toxicity.

Keywords::

• essential thrombocythemia
• FLT3 inhibitor
• JAK2 inhibitor
• myelofibrosis
• myeloproliferative neoplasms
• pacritinib
• polycythemia vera
• ruxolitinib
• SB1518

Financial & competing interests disclosure

RS Komrokji receives clinical research funding from Celgene, Incyte and GlaxoSmithKline and serves as a consultant for Celgene. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Pacritinib is a dual JAK2 and FLT3 inhibitor that has shown encouraging activity in Phase I/II trials in patients with myelofibrosis and is currently the subject of two Phase III trials versus standard therapy.

• Pacritinib is relatively well tolerated, and toxicities reported thus far are mainly gastrointestinal in nature.

• Hematological toxicity of pacritinib appears to be less than other JAK2 inhibitors, which may create a unique niche for this drug.

• Like other approved JAK2 inhibitors or those being evaluated in clinical trials, pacritinib is effective in reducing spleen size and alleviating disease-related symptoms, but does not appear to reduce mutant allele burden substantially. Combination therapies with pacritinib are likely to be evaluated in the future and its activity and toxicity profile may dictate such combinations.