Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease.

Acute Disease Adolescent Adult Aged Child Female Glucocorticoids / therapeutic use Graft vs Host Disease / drug therapy Humans Janus Kinase Inhibitors / adverse effects Male Middle Aged Nitriles Pyrazoles / adverse effects Pyrimidines Stem Cell Transplantation / adverse effects Thrombocytopenia / chemically induced Transplantation, Homologous Young Adult

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
07 05 2020
Historique:
pubmed: 23 4 2020
medline: 20 5 2020
entrez: 23 4 2020
Statut: ppublish

Résumé

Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy. (Funded by Novartis; REACH2 ClinicalTrials.gov number, NCT02913261.).

Sections du résumé

BACKGROUND
Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD.
METHODS
We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56.
RESULTS
A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]).
CONCLUSIONS
Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy. (Funded by Novartis; REACH2 ClinicalTrials.gov number, NCT02913261.).

Identifiants

DOI: 10.1056/NEJMoa1917635 PMID: 32320566
pubmed: 32320566
doi: 10.1056/NEJMoa1917635
doi:

Substances chimiques

Glucocorticoids 0
Janus Kinase Inhibitors 0
Nitriles 0
Pyrazoles 0
Pyrimidines 0
ruxolitinib 82S8X8XX8H

Banques de données

ClinicalTrials.gov
['NCT02913261']

Types de publication

Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1800-1810

Investigateurs

Sung-Soo Yoon (SS)
Chulwon Jung (C)
Tobias Gedde-Dahl (T)
Marwan Shaheen (M)
Jose Antonio Perez Simon (JA)
Jose Valentin Garcia Gutierrez (JV)
Jaime Sanz Caballer (J)
Rafael Duarte Palomino (RD)
David Valcarcel Ferreiras (D)
Cristina Diaz de Heredia Rubio (C)
Mi Kwon (M)
Maria Del Carmen Martinez Munoz (M)
Soledad Gonzalez (S)
Matilde Rodriguez Ruiz (M)
Inmaculada Heras Fernando (I)
Maria Pascual Cascon (M)
Ana Sastre Urgelles (A)
Marta Gonzalez Vicent (M)
Jose Maria Fernandez Navarro (JM)
Yvonne Björk (Y)
Kristina Carlson (K)
Jih-Luh Tang (JL)
Su-Peng Yeh (SP)
Ronjon Chakraverty (R)
Robert Wynn (R)
Lajos Floro (L)
Brian Thomas Kornblit (BT)
Jason Butler (J)
David Ritchie (D)
John Kwan (J)
Jacqueline Fleming (J)
Duncan Purtill (D)
Georg Hopfinger (G)
Hildegard Greinix (H)
Johannes Clausen (J)
Dennis Kim (D)
Natasha Kekre (N)
Imran Ahmad (I)
Brian Leber (B)
Andrew Daly (A)
Gizelle Popradi (G)
Jennifer White (J)
Mohamed Elemary (M)
Gerard Socie (G)
Valérie Coiteux (V)
Patrice Chevallier (P)
Claude-Eric Bulabois (CE)
Helene Labussiere-Wallet (H)
Mohamad Mohty (M)
Pierre-Simon Rohrlich (PS)
Edouard Forcade (E)
Fabrice Larosa (F)
Sylvie Francois (S)
Stephanie N'Guyen Quoc (S)
Marie-Therese Rubio (MT)
Jean-Hughes Dalle (JH)
Marie Ouachee-Chardin (M)
Benedicte Bruno (B)
Anne Huynh (A)
Nathalie Fegueux (N)
Jerome Cornillon (J)
Pascal Turlure (P)
Nikolas von Bubnoff (N)
Georg-Nikolaus Franke (GN)
Friedrich Stoelzel (F)
Matthias Eder (M)
Arne Brecht (A)
Nicolaus Kroeger (N)
Nina-Kristin Steckel (NK)
Eva Wagner (E)
Guido Kobbe (G)
Wolfgang Bethge (W)
Matthias Stelljes (M)
Donald Bunjes (D)
Igor Blau (I)
Ingo Mueller (I)
Stefan Klein (S)
Christoph Schmid (C)
Lena Oevermann (L)
Herrad Baurmann (H)
Inken Hilgendorf (I)
Klaus Daniel Stachel (KD)
Yok-Lam Kwong (YL)
Ron Ram (R)
Batya Avni (B)
Moshe Yeshurun (M)
Tsila Zuckerman (T)
Riccardo Saccardi (R)
Paolo Corradini (P)
Franco Locatelli (F)
Alessandro Rambaldi (A)
Andrea Bacigalupo (A)
Attilio Olivieri (A)
Francesca Patriarca (F)
Giovanni Grillo (G)
Francesca Bonifazi (F)
Edoardo Lanino (E)
Attilio Rovelli (A)
Benedetto Bruno (B)
Domenico Russo (D)
Maurizio Musso (M)
Marco Zecca (M)
Franca Fagioli (F)
Angelo Michele Carella (AM)
Stefania Bregante (S)
Roberto Sorasio (R)
Takanori Teshima (T)
Koichi Miyamura (K)
Kiyoshi Ando (K)
Hirohisa Nakamae (H)
Yoshinobu Maeda (Y)
Tadakazu Kondo (T)
Masaya Okada (M)
Kazuhiko Kakihana (K)
Koji Kato (K)
Yasushi Onishi (Y)
Kentaro Fukushima (K)
Shuichi Taniguchi (S)
Takehiko Mori (T)
Takayuki Ishikawa (T)
Yoshihiro Inamoto (Y)
J Kuball (J)
C A Lindemans (CA)
Jan Vydra (J)
Achilleas Anagnostopoulos (A)
Zubeyde Ozkurt (Z)
Zafer Gulbas (Z)
Seckin Cagirgan (S)
Sinem Civriz Bozdag (S)
Penka Ganeva (P)
Dobrin Konstantinov (D)
Kazimierz Halaburda (K)
Jan Zaucha (J)
Gergely Krivà N (G)
Isabelina Ferreira (I)
Joao Forjaz de Lacerda (JF)
Alexey Maschan (A)
Elena Parovichnikova (E)

Commentaires et corrections

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Informations de copyright

Copyright © 2020 Massachusetts Medical Society.

Auteurs

Robert Zeiser (R)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Nikolas von Bubnoff (N)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Jason Butler (J)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Mohamad Mohty (M)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Dietger Niederwieser (D)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Reuven Or (R)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Jeff Szer (J)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Eva M Wagner (EM)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Tsila Zuckerman (T)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Bruyère Mahuzier (B)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Judith Xu (J)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Celine Wilke (C)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Kunal K Gandhi (KK)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

Gérard Socié (G)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), the Department of Hematology and Oncology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck (N.B.), the Department of Hematology and Oncology, University of Leipzig, Leipzig (D.N.), and the Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz (E.M.W.) - all in Germany; the Department of Bone Marrow Transplantation, Royal Brisbane and Women's Hospital, Brisbane, QLD (J.B.), and the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC (J.S.) - all in Australia; Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Sorbonne and INSERM Unité Mixte de Recherche (UMR) 938 (M.M.), and AP-HP, Hématologie-Transplantation, Hôpital St. Louis, Université de Paris and INSERM UMR 976 (G.S.), Paris, and Novartis Pharma, Rueil-Malmaison (B.M.) - all in France; the Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem (R.O.), and the Hematology Institute and Bone Marrow Transplantation, Clinical Research Institute at Rambam, Rambam Health Care Campus, Haifa (T.Z.) - both in Israel; Novartis Pharmaceuticals, East Hanover, NJ (J.X., K.K.G.); and Novartis Pharma, Basel, Switzerland (C.W.).

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questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie aigüe › Ruxolitinib for Glucocorticoid-Refractory...
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