title: Ruxolitinib versus standard therapy for the treatment of polycythemia vera.
abstract: BACKGROUND
  Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with polycythemia vera in a phase 2 study. We conducted a phase 3 open-label study to evaluate the efficacy and safety of ruxolitinib versus standard therapy in patients with polycythemia vera who had an inadequate response to or had unacceptable side effects from hydroxyurea.
  
  
  METHODS
  We randomly assigned phlebotomy-dependent patients with splenomegaly, in a 1:1 ratio, to receive ruxolitinib (110 patients) or standard therapy (112 patients). The primary end point was both hematocrit control through week 32 and at least a 35% reduction in spleen volume at week 32, as assessed by means of imaging.
  
  
  RESULTS
  The primary end point was achieved in 21% of the patients in the ruxolitinib group versus 1% of those in the standard-therapy group (P<0.001). Hematocrit control was achieved in 60% of patients receiving ruxolitinib and 20% of those receiving standard therapy; 38% and 1% of patients in the two groups, respectively, had at least a 35% reduction in spleen volume. A complete hematologic remission was achieved in 24% of patients in the ruxolitinib group and 9% of those in the standard-therapy group (P=0.003); 49% versus 5% had at least a 50% reduction in the total symptom score at week 32. In the ruxolitinib group, grade 3 or 4 anemia occurred in 2% of patients, and grade 3 or 4 thrombocytopenia occurred in 5%; the corresponding percentages in the standard-therapy group were 0% and 4%. Herpes zoster infection was reported in 6% of patients in the ruxolitinib group and 0% of those in the standard-therapy group (grade 1 or 2 in all cases). Thromboembolic events occurred in one patient receiving ruxolitinib and in six patients receiving standard therapy.
  
  
  CONCLUSIONS
  In patients who had an inadequate response to or had unacceptable side effects from hydroxyurea, ruxolitinib was superior to standard therapy in controlling the hematocrit, reducing the spleen volume, and improving symptoms associated with polycythemia vera. (Funded by Incyte and others; RESPONSE ClinicalTrials.gov number, NCT01243944.).
authors: From Azienda Ospedaliera-Universitaria Careggi, University of Florence, Florence (A.M.V.), Ospedale di Circolo e Fondazione Macchi, Varese (F. Passamonti), and University of Naples Federico II, Naples (F. Pane) - all in Italy; Hôpital Saint-Louis et Université Paris Diderot, Paris (J.J.K.); Johannes Wesling Clinic, Minden, Germany (M.G.); St. István and St. László Hospital and Semmelweis University, Budapest, Hungary (T.M.); Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia (S.D.); Guy's and St. Thomas' NHS Foundation Trust, London (C.N.H.); Ziekenhuis Netwerk Antwerpen Stuivenberg, Antwerp, Belgium (P.Z.); Mayo Clinic Cancer Center, Scottsdale, AZ (R.M.); Incyte, Wilmington, DE (S.H., M.M.J., W.G.); Novartis Pharmaceuticals, East Hanover, NJ (J.L., D.H.); Novartis Pharma, Basel, Switzerland (U.P.); and University of Texas M.D. Anderson Cancer Center, Houston (S.V.).
authors: Alessandro M
authors: AM
authors: Vannucchi
authors: Jean Jacques
authors: JJ
authors: Kiladjian
authors: Martin
authors: M
authors: Griesshammer
authors: Tamas
authors: T
authors: Masszi
authors: Simon
authors: S
authors: Durrant
authors: Francesco
authors: F
authors: Passamonti
authors: Claire N
authors: CN
authors: Harrison
authors: Fabrizio
authors: F
authors: Pane
authors: Pierre
authors: P
authors: Zachee
authors: Ruben
authors: R
authors: Mesa
authors: Shui
authors: S
authors: He
authors: Mark M
authors: MM
authors: Jones
authors: William
authors: W
authors: Garrett
authors: Jingjin
authors: J
authors: Li
authors: Ulrich
authors: U
authors: Pirron
authors: Dany
authors: D
authors: Habr
authors: Srdan
authors: S
authors: Verstovsek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001772:Blood Cell Count; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000627:therapeutic use; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D009929:Organ Size / Q000187:drug effects; D011087:Polycythemia Vera / Q000188:drug therapy*; D011720:Pyrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines; D012074:Remission Induction; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053612:Janus Kinases; D006918:Hydroxyurea
references: N Engl J Med. 2013 Apr 18;368(16):1555-6
references: 23594015
references: N Engl J Med. 2013 Jan 3;368(1):22-33
references: 23216616
references: Leuk Res. 2013 Sep;37(9):1041-5
references: 23827351
references: Expert Opin Emerg Drugs. 2013 Sep;18(3):393-404
references: 23968379
references: Leukemia. 2013 Sep;27(9):1874-81
references: 23739289
references: Leuk Lymphoma. 2013 Oct;54(10):2226-30
references: 23398206
references: Cancer. 2014 Feb 15;120(4):513-20
references: 24258498
references: Blood. 2014 Jun 12;123(24):3803-10
references: 24553173
references: J Nutr Biochem. 2014 Nov;25(11):1101-7
references: 25154570
references: Leuk Lymphoma. 2014 Dec;55(12):2685-90
references: 24524340
references: Blood. 2011 May 5;117(18):4706-15
references: 21389325
references: Am J Hematol. 2013 Jun;88(6):507-16
references: 23695894
references: Blood. 2012 Feb 9;119(6):1363-9
references: 22160617
references: Blood. 2002 Dec 15;100(13):4272-90
references: 12393615
references: N Engl J Med. 2004 Jan 8;350(2):114-24
references: 14711910
references: Am Fam Physician. 2004 May 1;69(9):2139-44
references: 15152961
references: Am J Med. 2004 Nov 15;117(10):755-61
references: 15541325
references: Blood. 2005 Apr 1;105(7):2664-70
references: 15585653
references: Blood. 2007 Mar 15;109(6):2446-52
references: 17105814
references: Blood. 2008 Oct 15;112(8):3065-72
references: 18650451
references: Leukemia. 2008 Nov;22(11):1990-8
references: 18843285
references: Blood. 2009 Jul 23;114(4):759-63
references: 19372254
references: J Clin Oncol. 2009 Nov 10;27(32):5418-24
references: 19826111
references: Med Oncol. 2010 Mar;27(1):105-7
references: 19225914
references: Br J Haematol. 2010 Mar;148(6):961-3
references: 19930182
references: Haematologica. 2011 Feb;96(2):315-8
references: 21173097
references: J Clin Oncol. 2011 Feb 20;29(6):761-70
references: 21205761
references: J Clin Oncol. 2011 Jun 10;29(17):2410-5
references: 21537037
references: J Clin Oncol. 2011 Oct 10;29(29):3907-13
references: 21911721