Ruxolitinib as an emerging treatment in myelofibrosis

Essential thrombocythemia, polycythemia vera, and myelofibrosis belong to the class of Bcr-Abl negative hematologic neoplasms, which arise in part from varying Janus kinase-2 (JAK2) cellular deregulation. With the development of novel tyrosine kinase inhibitors capable of successfully inhibiting JAK in vivo, an influx of JAK2 inhibitors has come under clinical investigation. Ruxolitinib (Jakafi((R)); Incyte Corporation, Wilmington, DE, USA) was the first of these compounds to gain US Food and Drug Administration approval in late 2011 for the treatment of intermediate-and high-risk myelofibrosis. Two Phase III clinical trials - Controlled Myelofibrosis Study with Oral JAK Inhibitor Treatment-I and -II (COMFORT-I and -II) -played key roles in the US Food and Drug Administration approval of ruxolitinib with successful demonstration of spleen reduction and symptom palliation. Well tolerated in most patients, common side effects include cytopenias and gastrointestinal toxicities. The majority of preliminary data appears to suggest that if administered in a dose-titrated fashion, ruxolitinib can be used safely in a clinical practice setting. Additionally, patients most likely to benefit from ruxolitinib treatment are those with moderate to severe constitutional symptoms or splenomegaly. Future studies are ongoing in applying ruxolitinib to other hematologic and solid tumor malignancies. More clinical experience is recommended before the utility of this medication in a routine clinical practice setting can be fully determined.