Pomalidomide and the growing role of immunomodulatory agents in the treatment of myelofibrosis

Introduction: Myelofibrosis (MF) is a myeloid malignancy that may arise de novo as primary MF or antecedent to essential thrombocythemia or polycythemia vera. Recent discoveries in the pathogenesis contributing to MF symptoms have led to various targeted therapies including the promising immunomodulator, pomalidomide (POM). Areas covered: Treatments for MF are directed at alleviating the burden of symptoms and transfusion dependence. Clinical trials investigating effects of thalidomide derivatives and JAK2 inhibitors on symptoms and cytopenias have demonstrated variable improvements. POM (Pomalyst®), a second-generation immunomodulatory agent (IMiD; Celgene Corp.®), has demonstrated efficacy in mediating the regenerative cellular propensities observed in autoimmune-mediated disorders, solid tumors, and hematological malignancies via its anti-inflammatory, antiangiogenic, and immunomodulatory effects. Studies of POM in MF have demonstrated efficacy in achieving transfusion independence and improving cytopenias while proving more tolerable than thalidomide and lenalidomide. Results from an active Phase III randomized trial are eagerly awaited. In this article, we review the application of IMiDs in the treatment of MF and discuss the emerging role of POM as a potential armament against MF symptoms. Search methodology included a comprehensive review of MEDLINE articles and annual meeting abstracts from the 2010-2013 American Society of Hematology and American Society of Clinical Oncology publications. Expert opinion: POM monotherapy improves cytopenias in MF with fewer side effects than other immunomodulators. POM in combination with JAK2 inhibitors and other agents may prove beneficial in targeting the complex aberrant signaling pathways inherent to MF.