Alessandro M Vannucchi1, Jean Jacques Kiladjian, Martin Griesshammer, Tamas Masszi, Simon Durrant, Francesco Passamonti, Claire N Harrison, Fabrizio Pane, Pierre Zachee, Ruben Mesa, Shui He, Mark M Jones, William Garrett, Jingjin Li, Ulrich Pirron, Dany Habr, Srdan Verstovsek. 1. 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.).
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.).
RCT Entities:
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: Holly L Geyer; Robyn M Scherber; Amylou C Dueck; Jean-Jacques Kiladjian; Zhijian Xiao; Stefanie Slot; Sonja Zweegman; Federico Sackmann; Ana Kerguelen Fuentes; Dolores Hernández-Maraver; Konstanze Döhner; Claire N Harrison; Deepti Radia; Pablo Muxi; Carlos Besses; Francisco Cervantes; Peter L Johansson; Bjorn Andreasson; Alessandro Rambaldi; Tiziano Barbui; Alessandro M Vannucchi; Francesco Passamonti; Jan Samuelsson; Gunnar Birgegard; Ruben A Mesa Journal: Blood Date: 2014-02-19 Impact factor: 22.113
Authors: Thomas Stauffer Larsen; Katrine F Iversen; Esben Hansen; Anders Bruun Mathiasen; Claus Marcher; Mikael Frederiksen; Herdis Larsen; Inge Helleberg; Caroline Hasselbalch Riley; Ole W Bjerrum; Dorthe Rønnov-Jessen; Michael Boe Møller; Karin de Stricker; Hanne Vestergaard; Hans Carl Hasselbalch Journal: Leuk Res Date: 2013-07-01 Impact factor: 3.156
Authors: Johanna Abelsson; Björn Andréasson; Jan Samuelsson; Malin Hultcrantz; Elisabeth Ejerblad; Berit Johansson; Robyn Emanuel; Ruben Mesa; Peter Johansson Journal: Leuk Lymphoma Date: 2013-07-29
Authors: A Tefferi; E Rumi; G Finazzi; H Gisslinger; A M Vannucchi; F Rodeghiero; M L Randi; R Vaidya; M Cazzola; A Rambaldi; B Gisslinger; L Pieri; M Ruggeri; I Bertozzi; N H Sulai; I Casetti; A Carobbio; G Jeryczynski; D R Larson; L Müllauer; A Pardanani; J Thiele; F Passamonti; T Barbui Journal: Leukemia Date: 2013-06-06 Impact factor: 11.528
Authors: F Perner; T M Schnöder; S Ranjan; D Wolleschak; C Ebert; M C Pils; S Frey; A Polanetzki; C Fahldieck; U Schönborn; B Schraven; B Isermann; T Fischer; F H Heidel Journal: Leukemia Date: 2015-08-05 Impact factor: 11.528
Authors: Junshik Hong; Ju Hyun Lee; Ja Min Byun; Ji Yun Lee; Youngil Koh; Dong-Yeop Shin; Jeong-Ok Lee; Sang Mee Hwang; Hyoung Soo Choi; Inho Kim; Sung-Soo Yoon; Soo-Mee Bang Journal: Blood Adv Date: 2019-11-26
Authors: Brady L Stein; Jason Gotlib; Murat Arcasoy; Marie Huong Nguyen; Neil Shah; Alison Moliterno; Catriona Jamieson; Daniel A Pollyea; Bart Scott; Martha Wadleigh; Ross Levine; Rami Komrokji; Rebecca Klisovic; Krishna Gundabolu; Patricia Kropf; Meir Wetzler; Stephen T Oh; Raul Ribeiro; Rita Paschal; Sanjay Mohan; Nikolai Podoltsev; Josef Prchal; Moshe Talpaz; David Snyder; Srdan Verstovsek; Ruben A Mesa Journal: J Natl Compr Canc Netw Date: 2015-04 Impact factor: 11.908