Evaluation of Ruxolitinib for Steroid-Refractory Chronic Graft-vs-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Key Points Question Is ruxolitinib an option for patients with steroid-refractory chronic graft-vs-host disease, and what characteristics are associated with treatment response? Findings In this case series of 41 patients with steroid-refractory chronic graft-vs-host disease who were treated with ruxolitinib, heavily pretreated patients could achieve meaningful responses with a favorable safety profile. No lung involvement and haploidentical donors were associated with response to ruxolitinib. Meaning In this study, monotherapy with ruxolitinib was associated with a meaningful response in patients with steroid-refractory chronic graft-vs-host disease, suggesting a possible therapeutic option for a serious disease with no currently accepted standard-of-care treatment.

[1]  He Huang,et al.  Ruxolitinib combined with etanercept induce a rapid response to corticosteroid‐refractory severe acute graft vs host disease after allogeneic stem cell transplantation: Results of a multi‐center prospective study , 2020, American journal of hematology.

[2]  Y. Nieto,et al.  Hematopoietic Cell Transplantation, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. , 2020, Journal of the National Comprehensive Cancer Network : JNCCN.

[3]  M. Arbushites,et al.  Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label, phase 2 trial. , 2020, Blood.

[4]  Haiyan Zhang.  Impact of donor and recipient characteristics on graft-versus-host disease and survival in HLA-matched sibling hematopoietic stem cell transplantation. , 2020, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[5]  J. Sierra,et al.  Ruxolitinib in refractory acute and chronic graft-versus-host disease: a multicenter survey study , 2019, Bone Marrow Transplantation.

[6]  K. Huelsman,et al.  Ruxolitinib as Salvage Therapy for Chronic Graft-versus-Host Disease. , 2019, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[7]  J. Dipersio,et al.  Ruxolitinib: a steroid sparing agent in chronic graft-versus-host disease , 2018, Bone Marrow Transplantation.

[8]  J. Dipersio,et al.  The Role of Janus Kinase Signaling in Graft-Versus-Host Disease and Graft Versus Leukemia. , 2017, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[9]  B. Blazar,et al.  Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy. , 2017, The New England journal of medicine.

[10]  B. Storer,et al.  An endpoint associated with clinical benefit after initial treatment of chronic graft-versus-host disease. , 2017, Blood.

[11]  J. Ritz,et al.  The Biology of Chronic Graft-versus-Host Disease: A Task Force Report from the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease. , 2017, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[12]  C. Lengerke,et al.  Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey , 2015, Leukemia.

[13]  C. Recordati,et al.  Pharmacologic Inhibition of JAK1/JAK2 Signaling Reduces Experimental Murine Acute GVHD While Preserving GVT Effects , 2015, Clinical Cancer Research.

[14]  J. Pérez-Simón.  Anti-common γ-chain antibody: one for all in GVHD. , 2015, Blood.

[15]  Yoshiya Tanaka,et al.  Tofacitinib, a JAK inhibitor, inhibits human B cell activation in vitro , 2014, Annals of the rheumatic diseases.

[16]  J. Ritz,et al.  Current issues in chronic graft-versus-host disease. , 2014, Blood.

[17]  S. Held,et al.  The JAK-inhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo. , 2013, Blood.

[18]  J. Dipersio,et al.  IFNγR signaling mediates alloreactive T-cell trafficking and GVHD. , 2012, Blood.

[19]  J. Ritz,et al.  Donor B-cell alloantibody deposition and germinal center formation are required for the development of murine chronic GVHD and bronchiolitis obliterans. , 2012, Blood.

[20]  M. Mohty,et al.  Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment of Chronic Graft-versus-Host Disease. , 2011, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[21]  E. Holler,et al.  Consensus conference on clinical practice in chronic graft-versus-host disease (GVHD): first-line and topical treatment of chronic GVHD. , 2010, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[22]  M. Nakahira,et al.  Differential requirements for JAK2 and TYK2 in T cell proliferation and IFN‐γ production induced by IL‐12 alone or together with IL‐18 , 2003, European journal of immunology.