Pegylated interferon therapy for patients with Philadelphia chromosome-negative myeloproliferative disorders

The conventional management of patients with high-risk Philadelphia chromosome-negative (Ph-negative) myeloproliferative disorders (MPDs) revolves around the administration of cytoreductive agents such as hydroxyurea, anagrelide, and recombinant human interferon alpha (IFN-alpha). IFN-alpha has shown significant activity in the treatment of chronic myelogenous leukemia (CML) and Ph-negative MDPs. However, the response rates of IFN-alpha therapy frequently have been hampered by high dropout rates due to side effects and inconvenient dosing schedules. Pegylated (PEG) IFN-alpha is formulated by covalently attaching polymers of ethylene glycol of large molecular weight to the native IFN-alpha molecule. Such chemical modification increases serum half-life, decreases renal excretion, and results in prolonged patient exposure to PEG-IFN-alpha, thus allowing for weekly administration while maintaining acceptable toxicity, tolerability, and activity profiles. The lack of adequate therapies for patients with MPDs and the superior pharmacokinetic and pharmacodynamic profile of PEG-IFN-alpha relative to standard IFN-alpha has prompted the investigation of the activity and safety of PEG-IFN-alpha in patients with essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis. We summarize the available data on the use of PEG-IFN-alpha in patients with Ph-negative MPDs.