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Emerging drugs for the treatment of Myelofibrosis.

INTRODUCTION: Myelofibrosis (MF) is a Philadelphia chromosome-negative myeloproliferative neoplasm (MPN). It can be sub-categorized into primary myelofibrosis, post polycythemia vera myelofibrosis and post essential thrombocythemia myelofibrosis. MF is a life-threatening hematologic malignancy characterized by dysregulation of the Janus associated kinase (JAK)/signal transducer and activator of transcription (STAT) signaling network and a heightened inflammatory state. Areas covered: We cover the pathogenesis, clinical features, new prognostic models, current treatment of MF and discuss agents in development. We also cover market review and health care costs associated with some of these therapies. Expert opinion: There are many ongoing clinical trials evaluating novel therapeutic approaches, including selective JAK inhibitors, histone deacetylase/DNA methyltransferase inhibitors, PI3K-inhibitors, Hedgehog/mammalian target of rapamycin (MTOR) inhibitors, anti-fibrotic agents, immunomodulators, monoclonal antibodies and immune checkpoint inhibitors. Ruxolitinib, a potent oral JAK1/JAK2 inhibitor remains the only Food and Drug Administration (FDA)-approved medicinal therapy for the treatment of MF. Unmet needs include alleviation of limiting thrombocytopenia and anemia, halting disease progression to acute leukemia, and extending survival. The development of biomarker driven clinical trials of mechanism based novel therapeutics will usher in a new era of advances in the treatment of this chronic and progressive myeloid malignancy.

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