title: Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey.
abstract: Despite major improvements in allogeneic hematopoietic cell transplantation over the past decades, corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) cause high mortality. Preclinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib. In this retrospective survey, 19 stem cell transplant centers in Europe and the United States reported outcome data from 95 patients who had received ruxolitinib as salvage therapy for SR-GVHD. Patients were classified as having SR-aGVHD (n=54, all grades III or IV) or SR-cGVHD (n=41, all moderate or severe). The median number of previous GVHD-therapies was 3 for both SR-aGVHD (1-7) and SR-cGVHD (1-10). The overall response rate was 81.5% (44/54) in SR-aGVHD including 25 complete responses (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). Of those patients responding to ruxolitinib, the rate of GVHD-relapse was 6.8% (3/44) and 5.7% (2/35) for SR-aGVHD and SR-cGVHD, respectively. The 6-month-survival was 79% (67.3-90.7%, 95% confidence interval (CI)) and 97.4% (92.3-100%, 95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and cytomegalovirus-reactivation were observed during ruxolitinib treatment in both SR-aGVHD (30/54, 55.6% and 18/54, 33.3%) and SR-cGVHD (7/41, 17.1% and 6/41, 14.6%) patients. Ruxolitinib may constitute a promising new treatment option for SR-aGVHD and SR-cGVHD that should be validated in a prospective trial.
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Zeiser
authors.affiliation: Department of Hematology, Oncology and Immunology, Philipps University Marburg, and University Medical Center Giessen and Marburg, Marburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Burchert
authors.affiliation: Division of Hematology, University Hospital of Basel, Basel, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Lengerke
authors.affiliation: III Department of Internal Medicine, Technical University of Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Verbeek
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Maas-Bauer
authors.affiliation: Department of Hematology, Oncology and Immunology, Philipps University Marburg, and University Medical Center Giessen and Marburg, Marburg, Germany.
authors.forename: S K
authors.initials: SK
authors.lastname: Metzelder
authors.affiliation: III Department of Internal Medicine, Technical University of Munich, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Spoerl
authors.affiliation: Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital Essen, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Ditschkowski
authors.affiliation: Division of Hematology, University Hospital of Basel, Basel, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Ecsedi
authors.affiliation: Department of Hematology and Oncology, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Sockel
authors.affiliation: Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Ayuk
authors.affiliation: Department of Internal Medicine II, University Hospital, Frankfurt/Main, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ajib
authors.affiliation: Hematology Stem cell transplant Unit, Saint Louis Hospital, APHP, Paris, France.
authors.forename: F S
authors.initials: FS
authors.lastname: de Fontbrune
authors.affiliation: Department of Stem Cell Transplantation, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: I-K
authors.initials: IK
authors.lastname: Na
authors.affiliation: Department of Stem Cell Transplantation, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Penter
authors.affiliation: Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Holtick
authors.affiliation: Medical Clinic III, Oncology, Hematology and Rheumatology, University Hospital Bonn (UKB), Bonn, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Wolf
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, Universitätsklinikum Düsseldorf, Düsseldorf, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Schuler
authors.affiliation: Department of Bone Marrow Transplantation, Stanford University Medical School, Stanford, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Meyer
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Apostolova
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bertz
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Marks
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Lübbert
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Wäsch
authors.affiliation: Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Scheid
authors.affiliation: Department of Hematology and Oncology, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Stölzel
authors.affiliation: Department of Hematology and Oncology, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Ordemann
authors.affiliation: Department of Internal Medicine II, University Hospital, Frankfurt/Main, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Bug
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, Universitätsklinikum Düsseldorf, Düsseldorf, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kobbe
authors.affiliation: Department of Bone Marrow Transplantation, Stanford University Medical School, Stanford, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Negrin
authors.affiliation: Department of Internal Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Brune
authors.affiliation: Department of Bone Marrow Transplantation, Patras University Medical School, Patras, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Spyridonidis
authors.affiliation: Department of Pathology, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schmitt-Gräff
authors.affiliation: Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: van der Velden
authors.affiliation: Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Huls
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Würzburg, Würzburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Mielke
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Würzburg, Würzburg, Germany.
authors.forename: G U
authors.initials: GU
authors.lastname: Grigoleit
authors.affiliation: Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Kuball
authors.affiliation: Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA.
authors.forename: R
authors.initials: R
authors.lastname: Flynn
authors.affiliation: Clinical Trials Unit, Department of Hematology, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Ihorst
authors.affiliation: Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA.
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA.
authors.forename: B R
authors.initials: BR
authors.lastname: Blazar
authors.affiliation: Department of Stem Cell Transplantation, Charité University Medicine Berlin, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Arnold
authors.affiliation: Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kröger
authors.affiliation: Division of Hematology, University Hospital of Basel, Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Passweg
authors.affiliation: Division of Hematology, University Hospital of Basel, Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Halter
authors.affiliation: Hematology Stem cell transplant Unit, Saint Louis Hospital, APHP, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Socié
authors.affiliation: Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital Essen, Essen, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Beelen
authors.affiliation: III Department of Internal Medicine, Technical University of Munich, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Peschel
authors.affiliation: Department of Hematology, Oncology and Immunology, Philipps University Marburg, and University Medical Center Giessen and Marburg, Marburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Neubauer
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Finke
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Duyster
authors.affiliation: Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Freiburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: von Bubnoff
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D019337:Hematologic Neoplasms / Q000150:complications* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D008297:Male; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles; D011379:Prognosis; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D012008:Recurrence; D012189:Retrospective Studies; D016879:Salvage Therapy; D015996:Survival Rate; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053612:Janus Kinases