Profle of pomalidomide and its potential in the treatment of myelofbrosis

Myelofbrosis, a Philadelphia-negative myeloproliferative neoplasm, is in a new treatment era after the discovery of the JAK2V617F mutation in 2005. JAK inhibitors boast improvements in disease-related symptoms, splenomegaly, and overall survival; however, treatment of myelofbrosis remains a challenge, given the lack of improvement in cytopenias with these agents. Second-generation immunomodulatory agents, such as pomalidomide, have shown effcacy in myelofbrosis-associated anemia within multiple clinical trials. Five major pomalido-mide clinical trials have been completed to date, and demonstrate tolerability and effcacy with low-dose pomalidomide (0.5 mg/day) in the treatment of myelofbrosis, and no clinical beneft of elevated dosing regimens ($2.5 mg/day). Anemia responses ranged from 17% to 36% as per the International Working Group for Myelofbrosis Research and Treatment consensus guidelines, while improvements in splenomegaly were rare, and observed in,1% of most clinical trials. In comparison with earlier immunomodulatory agents, pomalidomide was associated with an improved toxicity profle, with substantially lower rates of myelosuppression and neuropathy. Given the low overall response rate to pomalidomide as a single agent, combination strategies are of particular interest for future studies. Pomalidomide is currently being tested in combination with ruxolitinib, and other novel combinations are likely on the horizon.