title: Efficacy of ruxolitinib for myelofibrosis.
abstract: BACKGROUND
  The discovery of the activating JAK2 V617F mutation in patients with myelofibrosis (MF) led to the development of JAK2 inhibitors. The first such inhibitor to enter clinical trials was ruxolitinib . This review summarizes preclinical and clinical data of ruxolitinib in MF.
  
  
  METHODS
  A literature search through Medline employing the terms 'ruxolitinib,' 'INCB018424' and 'myelofibrosis' was undertaken. The results from Phase I/II studies in patients with MF showed that ruxolitinib led to durable improvements in splenomegaly, and symptoms associated with MF. Two Phase III trials have compared ruxolitinib against placebo and best available therapy, and in both studies ruxolitinib demonstrated superior rates of spleen control and symptom improvement, and additional analysis demonstrated a survival benefit with ruxolitinib treatment. The main toxicities seen with ruxolitinib are cytopenias, which are managed with dose adjustments. Recent reports documented sporadic cases of immunosuppression-related infections. Ruxolitinib is the first drug ever approved for the therapy of patients with MF.
  
  
  CONCLUSIONS
  Understanding the factors that predict the rate and duration of response to ruxolitinib would improve our ability to manage patients treated with this medication. Clinical trials combining ruxolitinib with novel compounds that are also active in MF will further improve therapy for this disease.
authors.affiliation: Hospital Israelita Albert Einstein, Hematology and Oncology Center , São Paulo, SP , Brazil.
authors.forename: Fabio P S
authors.initials: FP
authors.lastname: Santos
authors.forename: Srdan
authors.initials: S
authors.lastname: Verstovsek
mesh_terms: D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000235:genetics; D009154:Mutation; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000473:pathology; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D013163:Splenomegaly / Q000188:drug therapy; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053614:Janus Kinase 2
keywords: JAK2 V617F; clinical study; myelofibrosis; ruxolitinib