title: Emerging treatments for classical myeloproliferative neoplasms.
abstract: There has been a major revolution in the management of patients with myeloproliferative neoplasms (MPN), and in particular those with myelofibrosis and extensive splenomegaly and symptomatic burden, after the introduction of the JAK1 and JAK2 inhibitor ruxolitinib. The drug also has been approved as second-line therapy for polycythemia vera (PV). However, the therapeutic armamentarium for MPN is still largely inadequate for coping with patients' major unmet needs, which include normalization of life span (myelofibrosis and some patients with PV), reduction of cardiovascular complications (mainly PV and essential thrombocythemia), prevention of hematological progression, and improved quality of life (all MPN). In fact, none of the available drugs has shown clear evidence of disease-modifying activity, even if some patients treated with interferon and ruxolitinib showed reduction of mutated allele burden, and ruxolitinib might extend survival of patients with higher-risk myelofibrosis. Raised awareness of the molecular abnormalities and cellular pathways involved in the pathogenesis of MPN is facilitating the development of clinical trials with novel target drugs, either alone or in combination with ruxolitinib. Although for most of these molecules a convincing preclinical rationale was provided, the results of early phase 1 and 2 clinical trials have been quite disappointing to date, and toxicities sometimes have been limiting. In this review, we critically illustrate the current landscape of novel therapies that are under evaluation for patients with MPN on the basis of current guidelines, patient risk stratification criteria, and previous experience, looking ahead to the chance of a cure for these disorders.
authors.affiliation: Center of Research and Innovation of Myeloproliferative Neoplasms, Azienda Ospedaliera Universitaria Careggi and Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; and.
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.affiliation: Department of Haematology, Guy's and St Thomas' National Health Service Foundation Trust, London, United Kingdom.
authors.forename: Claire N
authors.initials: CN
authors.lastname: Harrison
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009570:Nitriles; D011087:Polycythemia Vera / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D011788:Quality of Life; D016019:Survival Analysis; D013920:Thrombocythemia, Essential / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D016898:Interferon-alpha; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; C507924:JAK2 protein, human; D053614:Janus Kinase 2