Safety and Effectiveness of Vedolizumab in Patients with Steroid- Refractory Gastrointestinal Acute Graft-versus-Host Disease: A Retrospective Record Review Yngvar Fløisand 1, *, Vladimir Lj Lazarevic 2 , Johan Maertens 3 , Jonas Mattsson 4 , Nirav N. Shah 5 , Pierre Zach  ee 6 , Aliki Taylor 7 , Mona Akbari 8 , Syed Quadri 8 , Andrejus Parfionovas 8 , Yi-Bin Chen 9 1 Department of Hematology, Oslo University Hospital, Oslo, Norway 2 Department of Hematology, Oncology and Radiation Physics, Ska  ne University Hospital, Lund University, Lund, Sweden 3 Department of Hematology, University Hospitals Leuven, Leuven, Belgium 4 Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden 5 Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin 6 Hematology Service, ZNA Stuivenberg, Antwerp, Belgium 7 Takeda Development Centre Europe Ltd, London, UK 8 Takeda Pharmaceuticals International Co., Cambridge, Massachusetts 9 Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, Massachusetts Article history: Received 13 September 2018 Accepted 13 November 2018 ABSTRACT Allogeneic hematopoietic cell transplantation (allo-HCT) can be curative in patients with hematologic malignan- cies but carries a significant risk of graft-versus-host disease (GVHD). There are no standard treatments for steroid-refractory (SR) gastrointestinal (GI) acute GVHD (aGVHD). This multicenter, international, retrospective medical record review aimed to evaluate the off-label use of vedolizumab, a gut-selective immunomodulator, for treating SR GI aGVHD. Data were collected from patients’ medical records; criteria for extraction included no more than 1 allo-HCT and at least 1 dose of vedolizumab as treatment for SR GI aGVHD (ie, stage 1 to 4 GI aGVHD following 1 previous treatment regimen(s) containing 1 mg/kg methylprednisolone or equivalent). Descriptive analyses of response rate, overall survival (OS), and serious adverse effects (SAEs) were performed. Twenty-nine patients were identified from 7 sites who had received 1 to 10 doses of vedolizumab 300 mg i.v. (median 3 doses) as treatment for SR GI aGVHD. The overall response rate at 6 to 10 weeks after vedolizumab initiation was 64%, and OS at 6 months was 54%. There were 29 SAEs, including 12 infections; 3 SAEs were considered possibly related to vedolizumab, 2 of which were infections. Thirteen SAEs were fatal, 1 of which was possibly vedolizumab- related. There were 8 nonserious infections and 1 serious infection with confirmed GI origin in 8 patients; there was no apparent pattern in the timing of these infections relative to the initiation of vedolizumab treatment. Further data on the efficacy and safety of vedolizumab in this setting from prospective trials are needed. © 2018 American Society for Blood and Marrow Transplantation. This is an open access article under the CC BY- NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/) Key Words: Safety Effectiveness Vedolizumab Steroid-refractory gastrointestinal acute graft-versus-host disease Retrospective record review INTRODUCTION Allogeneic hematopoietic cell transplantation (allo-HCT) can be curative in patients with hematologic malignancies or benign hematologic conditions, but its success is limited by the development of graft-versus-host disease (GVHD) [1,2]. Acute GVHD (aGVHD) most commonly involves the skin, liver, and gastrointestinal (GI) tract [3,4]. aGVHD of grade II-IV and grade III-IV have been reported in 39% to 71% and 14% to 32% of allo- HCT recipients, respectively, even with standard methods of GVHD prophylaxis [5,6]. Skin is the most commonly affected organ [7], but up to 60% of patients have GI involvement, which may result in persistent anorexia, secretory diarrhea, abdominal pain, and/or hemorrhage [8]. A study of 1462 patients who underwent allo-HCT between January 2000 and December 2005 found that 8% of patients developed stage 3 or 4 GI aGVHD and had an overall survival (OS) of 25% at 2 years [9]. Other studies have demonstrated that grade III-IV aGVHD with GI tract involvement is associated with very high overall mortality (70% to 90%) [6]. Treatment options for patients with aGVHD are limited. Corticosteroid therapy is most often used as first-line treatment in patients with grade II or higher aGVHD; however, this is Financial disclosure: See Acknowledgments on page 726. * Correspondence and reprint requests: Yngvar Fløisand, MD, Department of Hematology, Oslo University Hospital, Rikshospitalet, Room C6 2016, N-0027 Oslo, Norway. E-mail address: yfloisan@ous-hf.no (Y. Fløisand). https://doi.org/10.1016/j.bbmt.2018.11.013 1083-8791/© 2018 American Society for Blood and Marrow Transplantation. This is an open access article under the CC BY-NC-ND license. (http://creativecommons.org/licenses/by-nc-nd/4.0/) Biol Blood Marrow Transplant 25 (2019) 720727 Biology of Blood and Marrow Transplantation journal homepage: www.bbmt.org