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858 Treatment of Corticosteroid-Refractory Graft-Versus-Host Disease with Ruxolitinib in 95 Patients

Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution
Program: Oral and Poster Abstracts
Type: Oral
Session: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Clinical Trials
Monday, December 7, 2015: 5:45 PM
W230, Level 2 (Orange County Convention Center)

Robert Zeiser, MD1, Andreas Burchert, MD2, Claudia Lengerke, MD3, Mareike Verbeek4*, Kristina Maas-Bauer, MD5*, Stephan Metzelder, MD6*, Silvia Spoerl, MD7*, Markus Ditschkowski, MD8*, Matyas Ecsedi, MD9*, Katja Sockel, MD10*, Francis Ayuk, M.D.11*, Salem Ajib, MD12*, Flore Sicre de Fontbrune, MD13*, Il-Kang Na, MD14*, Livius Penter, MD15*, Udo Holtick, MD, PhD16*, Dominik Wolf, MD17*, Esther Schuler, MD18*, Everett Meyer, MD, PhD19, Petya Apostolova, MD20*, Hartmut Bertz, MD21*, Reinhard Marks22, Michael Luebbert, MD23*, Ralph M. Waesch, MD, PhD24, Christof Scheid25, Friedrich Stölzel, MD26*, Rainer Ordemann, MD27*, Gesine Bug, MD28*, Guido Kobbe, MD29*, Robert S. Negrin, MD30, Mats L Brune31, Alexandros Spyridonidis32, Annette Schmitt-Graeff, MD33*, Walter van der Velden, MD34*, Gerwin Huls, MD, PhD35*, Stephan Mielke, MD36, Goetz Ulrich Grigoleit, MD37*, Jurgen Kuball, MD PhD38, Ryan P Flynn, PhD39*, Gabriele Ihorst, PhD40*, Jing Du41, Bruce R. Blazar, MD42, Renate Arnold, MD15, Nicolaus Kröger, MD43*, Joerg Halter, MD44*, Gerard Socie45, Dietrich Beelen, MD46, Christian Peschel, MD47, Andreas Neubauer, MD6, Juergen Finke, MD48, Justus Duyster, MD, PhD49* and Nikolas von Bubnoff, MD23*

1Department of Hematology, Oncology and Stem Cell Transplantation, University Medical Center Freiburg, Freiburg, Germany
2Hem./Onc./Immunology, Philips Univ. Marburg, Marburg, Germany
3Division of Hematology, University Hospital Basel, Basel, Switzerland
4III. Department of Internal Medicine, Hematology and Medical Oncology, Technische Universität München, Munich, Germany
5Freibrug University Medical Center, Freiburg, Germany
6Dept. Hematology, Oncology, Immunology, Philipps University of Marburg, Medical Center of the University Giessen and Marburg, Marburg, Germany
7III Department of Internal Medicine, Technical University of Munich, Munich, Germany
8Department of Bone Marrow Transplantation, West German Cancer Center, University Hospital Essen, Essen, Germany
9University Hospital Basel, Division of Hematology, Basel, Basel, Switzerland
10Medizinische Klinik I, Universitaetsklinikum C.G.Carus, Dresden, Germany
11University Medical Center Hamburg-Eppendorf, Hamburg, Germany
12University Hospital, Frankfurt/Main, Frankfurt a.M, Germany
13Hematology/Transplantation, Hôpital Saint Louis, Paris, France
14Hematology and Oncology, Charité University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany
15Department of Stem Cell Transplantation, Charité University Medicine Berlin, Berlin, Germany
16Department of Internal Medicine I, University Hospital Cologne, Cologne, Germany
17Internal Medicine III, Oncology, Hematology and Rheumatology, University Clinic Bonn, Bonn, Germany
18Department of Hematology, Oncology and Clinical Immunology, Universitätsklinikum Düsseldorf, Düsseldorf,, Düsseldorf, Germany
19Division of Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA
20Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center,, Freiburg, Germany
21University Medical Center Freiburg, Freiburg, Germany
22Department of Hematology and Oncology, University Medical Center Freiburg, Freiburg, Germany
23Department of Hematology, Oncology and Stem Cell Transplantation, University of Freiburg Medical Center, Freiburg, Germany
24Department of Hematology&Oncology+Comprehensive Cancer Center Freiburg (CCCF), University of Freiburg Medical Center, Freiburg, Germany
25University of Cologne, Cologne, Germany
26Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany
27University Hospital TU Dresden, Dresden, Germany
28Department of Medicine, Hematology/Oncology, University of Frankfurt, Frankfurt, Germany
29Dept. of Hematology, Oncology and clinical Immunology, Heinrich-Heine University Duesseldorf, Duesseldorf, Germany
30Division of Blood and Marrow Transplantation, Stanford University, Stanford, CA
31Center for Hematopoietic Cell Transplantation, Sahlgrenska University Hospital, Goeteborg, Sweden
32Haematology Division, Patras University Medical School, University Hospital, Patras, Greece
33Department of Pathology, University Medical Center Freiburg, ALU Freiburg, Freiburg, Germany
34Haematology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
35Department of Hematology, Radboud university medical center, Nijmegen, Netherlands
36University of Würzburg, Würzburg, Germany
37Department of Internal Medicine II, Division of Hematology and Medical Oncology, Wuerzburg University Medical Center, Wuerzburg, Germany
38Hematology, University Medical Center Utrecht, Utrecht, Netherlands
39Department of Pediatrics, Division of Hematology, Oncology, and Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN
40Clinical Trials Unit, University of Freiburg Medical Center, Freiburg, Germany
41University of Minnesota, Minneapolis, MN
42Division of Pediatrics, Department of Medicine, University of Minnesota Cancer Center, Minneapolis, MN
43University Medical Center, Hamburg, Germany
44Hematology, University Hospital Basel, Basel, Switzerland
45St-Louis Hospital, Paris, France
46Department of Stem Cell Transplantation, University Medical Center Essen, Essen, Germany
47Department of Internal Medicine III, Technical University of Munich, Munich, Germany
48Hematology/Oncology, University Medical Center Freiburg, Freiburg, Germany
49Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Albert Ludwigs University (ALU) Freiburg, Freiburg, Germany

Background: Allogeneic hematopoietic cell transplantation is a potentially curative therapy for patients with hematological malignancies. However a fraction of patients will develop corticosteroid-refractory (SR) acute (a) and chronic (c) graft-versus-host disease (GVHD) which both cause a high mortality and impaired quality of life. Pre-clinical evidence indicates the potent anti-inflammatory properties of the JAK1/2 inhibitor ruxolitinib by modification of T cells and dendritic cells.

Methods: In this retrospective analysis, 19 stem cell transplant centers in Europe and the United States reported clinical 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 grade 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 median follow-up times were 26.5 (3-106) for SR-aGVHD and 22.4 (3-135) weeks for SR-cGVHD-patients.

Results: The ORR was 81.5% (44/54) in SR-aGVHD including 25 CRs (46.3%), while for SR-cGVHD the ORR was 85.4% (35/41). The median time to response was 1.5 (1-11) and 3 (1-25) weeks after initiation of ruxolitinib treatment in SR-aGVHD and SR-cGVHD, respectively. 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% CI) and 97.4% (92.3%-100%,95% CI) for SR-aGVHD and SR-cGVHD, respectively. Cytopenia and CMV 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. Relapse of the underlying malignancy occurred in 9.3% (5/54) and 2.4% (1/41) of the patients with SR-aGVHD or SR-cGVHD, respectively.

Conclusion: Ruxolitinib constitutes a promising new treatment option for SR-aGVHD and SR-cGVHD. Its activity in SR-aGVHD and SR-cGVHD should be validated in a prospective trials in both, SR-aGvHD and cGvHD.

Disclosures: Bertz: GILEAD Sciences: Honoraria , Membership on an entity’s Board of Directors or advisory committees , Research Funding . Bug: TEVA Oncology, Astellas: Other: Travel Grant ; NordMedica, Boehringer Ingelheim, Gilead: Membership on an entity’s Board of Directors or advisory committees ; Celgene, Novartis: Research Funding . Negrin: Regimmune: Research Funding .

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