title: Ruxolitinib: an oral Janus kinase 1 and Janus kinase 2 inhibitor in the management of myelofibrosis.
abstract: Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are referred to as the classic Philadelphia chromosome (BCR-ABL1)-negative myeloproliferative neoplasms. Although each has distinct pathologic features, all 3 display alterations in Janus kinase (JAK) signal transduction activator of transcription signaling. Myelofibrosis is the most serious of the 3, associated with shortened survival (median survival, 5-7 years); bone marrow failure with anemia; progressive splenomegaly; and chronic, burdensome symptoms, including fatigue, night sweats, itching, abdominal discomfort, loss of appetite/early satiety, unintentional weight loss, and bone, chest, and abdominal pain. Treatments for MF have been mainly palliative, with the exception of allogeneic stem cell transplantation, which, although potentially curative, is feasible only in a small subpopulation of patients. In November 2011, ruxolitinib, an inhibitor of JAK1 and JAK2, was approved by the US Food and Drug Administration for the treatment of intermediate- or high-risk MF, including primary MF, post-PV MF, and post-ET MF. In clinical trials, ruxolitinib was shown to reduce spleen volume and improve MF-related symptoms and quality-of-life measures. Evidence also suggests that ruxolitinib therapy has a survival advantage over placebo and best available therapy. Thrombocytopenia and anemia were the most common adverse events with treatment. Ongoing trials are assessing the efficacy and safety of ruxolitinib therapy in patients with PV and ET.
authors: Leukemia Department, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. sverstov@mdanderson.org
authors: Srdan
authors: S
authors: Verstovsek
mesh_terms: D006801:Humans; D053613:Janus Kinase 1 / Q000037:antagonists & inhibitors*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000188:drug therapy*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines; D013154:Spleen / Q000473:pathology*; D013163:Splenomegaly / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053613:Janus Kinase 1; D053614:Janus Kinase 2
references: Blood Rev. 2011 Sep;25(5):229-37
references: 21742423
references: N Engl J Med. 2012 Mar 1;366(9):787-98
references: 22375970
references: Blood. 2009 Mar 26;113(13):2895-901
references: 18988864
references: N Engl J Med. 2011 Oct 13;365(15):1455-7
references: 21995409
references: Drug Metab Dispos. 2010 Nov;38(11):2023-31
references: 20699411
references: ScientificWorldJournal. 2011 May 26;11:1131-7
references: 21623459
references: Platelets. 2004 Mar;15(2):67-84
references: 15154599
references: Nat Rev Drug Discov. 2011 Feb;10(2):127-40
references: 21283107
references: Leuk Res. 2009 Sep;33(9):1199-203
references: 19250674
references: N Engl J Med. 2012 May 24;366(21):2031; author reply 2032-4
references: 22621633
references: Blood. 2009 Jul 30;114(5):937-51
references: 19357394
references: Blood. 2009 Dec 17;114(26):5264-70
references: 19812383
references: Clin Cancer Res. 2012 Jun 15;18(12):3212-7
references: 22544377
references: Biol Blood Marrow Transplant. 2007 Mar;13(3):355-65
references: 17317589
references: J Clin Pharmacol. 2011 Dec;51(12):1644-54
references: 21257798
references: N Engl J Med. 2010 Sep 16;363(12):1117-27
references: 20843246
references: N Engl J Med. 2012 Mar 1;366(9):799-807
references: 22375971
references: CA Cancer J Clin. 2009 May-Jun;59(3):171-91
references: 19369682
references: Haematologica. 2011 Feb;96(2):183-6
references: 21282719
references: N Engl J Med. 2012 May 24;366(21):2032; author reply 2032-5
references: 22621635
references: Br J Haematol. 2012 Apr;157(1):75-85
references: 22280409
references: Blood. 2012 Aug 9;120(6):1202-9
references: 22718840
references: J Clin Oncol. 2011 Feb 20;29(6):761-70
references: 21205761
references: Hematology Am Soc Hematol Educ Program. 2011;2011:222-30
references: 22160038