[논문]Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial

Jagasia, Madan; Perales, Miguel-Angel; Schroeder, Mark A.; Ali, Haris; Shah, Nirav N.; Chen, Yi-Bin; Fazal, Salman; Dawkins, Fitzroy W.; Arbushites, Michael C.; Tian, Chuan; Connelly-Smith, Laura; Howell, Michael D.; Khoury, H. Jean

doi:10.1182/blood.2020004823

Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial 원문보기

Blood, v.135 no.20, 2020년, pp.1739 - 1749

Jagasia, Madan (Vanderbilt University Medical Center, Nashville, TN) , Perales, Miguel-Angel , Schroeder, Mark A. (Memorial Sloan-Kettering Cancer Center, New York, NY) , Ali, Haris , Shah, Nirav N. (Section of Blood and Marrow Transplant, Division of Oncology, Department of Medicine, Washington University, St. Louis, MO) , Chen, Yi-Bin , Fazal, Salman (City of Hope, Duarte, CA) , Dawkins, Fitzroy W. , Arbushites, Michael C. (Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI) , Tian, Chuan , Connelly-Smith, Laura (Massachusetts General Hospital, Boston, MA) , Howell, Michael D. , Khoury, H. Jean (Allegheny Health Network, Pittsburgh, PA)

Abstract ▼ AI-Helper

AbstractPatients who develop steroid-refractory acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation have poor prognosis, highlighting an unmet therapeutic need. In this open-label phase 2 study (ClinicalTrials.gov identifier: NCT02953678), patients aged at least 12 years with grades II to IV steroid-refractory aGVHD were eligible to receive ruxolitinib orally, starting at 5 mg twice daily plus corticosteroids, until treatment failure, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) at day 28; the key secondary end point was duration of response (DOR) at 6 months. As of 2 July 2018, 71 patients received at least 1 dose of ruxolitinib. Forty-eight of those patients (67.6%) had grade III/IV aGVHD at enrollment. At day 28, 39 patients (54.9%; 95% confidence interval, 42.7%-66.8%) had an overall response, including 19 (26.8%) with complete responses. Best ORR at any time was 73.2% (complete response, 56.3%). Responses were observed across skin (61.1%), upper (45.5%) and lower (46.0%) gastrointestinal tract, and liver (26.7%). Median DOR was 345 days. Overall survival estimate at 6 months was 51.0%. At day 28, 24 (55.8%) of 43 patients receiving ruxolitinib and corticosteroids had a 50% or greater corticosteroid dose reduction from baseline. The most common treatment-emergent adverse events were anemia (64.8%), thrombocytopenia (62.0%), hypokalemia (49.3%), neutropenia (47.9%), and peripheral edema (45.1%). Ruxolitinib produced durable responses and encouraging survival compared with historical data in patients with steroid-refractory aGVHD who otherwise have dismal outcomes. The safety profile was consistent with expectations for ruxolitinib and this patient population.

참고문헌 (31)

Nat Rev Immunol Blazar 12 6 443 2012 10.1038/nri3212 Advances in graft-versus-host disease biology and therapy

상세보기
D’Souza A , FrethamC. Current uses and outcomes of hematopoietic cell transplantation (HCT): 2018 summary slides. https://www.cibmtr.org/ReferenceCenter/SlidesReports/SummarySlides/_layouts/15/WopiFrame.aspx?sourcedoc=/ReferenceCenter/SlidesReports/SummarySlides/Documents/2018%20Summary%20Slides%20-%20final%20-%20for%20web%20posting.pptx&action=default. Accessed 8 October 2019.
Blood Jagasia 119 1 296 2012 10.1182/blood-2011-06-364265 Risk factors for acute GVHD and survival after hematopoietic cell transplantation

상세보기
N Engl J Med Gooley 363 22 2091 2010 10.1056/NEJMoa1004383 Reduced mortality after allogeneic hematopoietic-cell transplantation

상세보기
N Engl J Med Zeiser 377 22 2167 2017 10.1056/NEJMra1609337 Acute graft-versus-host disease - biologic process, prevention, and therapy

상세보기
Biol Blood Marrow Transplant Lazaryan 22 1 134 2016 10.1016/j.bbmt.2015.09.008 Risk factors for acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation with umbilical cord blood and matched sibling donors

상세보기
Haematologica Inamoto 99 2 385 2014 10.3324/haematol.2013.093062 Response endpoints and failure-free survival after initial treatment for acute graft-versus-host disease

상세보기
Biol Blood Marrow Transplant Martin 18 8 1150 2012 10.1016/j.bbmt.2012.04.005 First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation

상세보기
Biol Blood Marrow Transplant Arai 8 3 155 2002 10.1053/bbmt.2002.v8.pm11939605 Poor outcome in steroid-refractory graft-versus-host disease with antithymocyte globulin treatment

상세보기
Biol Blood Marrow Transplant Xhaard 18 3 406 2012 10.1016/j.bbmt.2011.06.012 Steroid-refractory acute GVHD: lack of long-term improved survival using new generation anticytokine treatment

상세보기
Incyte Corporation . FDA approves Jakafi® (ruxolitinib) for the treatment of patients with acute graft-versus-host disease [press release]. https://investor.incyte.com/news-releases/news-release-details/fda-approves-jakafir-ruxolitinib-treatment-patients-acute-graft. Accessed 3 June 2019.
Biol Blood Marrow Transplant Schroeder 24 6 1125 2018 10.1016/j.bbmt.2017.12.797 The role of Janus kinase signaling in graft-versus-host disease and graft versus leukemia

상세보기
Leukemia Zeiser 29 10 2062 2015 10.1038/leu.2015.212 Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey

상세보기
Blood Spoerl 123 24 3832 2014 10.1182/blood-2013-12-543736 Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease

상세보기
Blood Zeiser 128 22 4561 2016 10.1182/blood.V128.22.4561.4561 Long-term follow-up of patients with corticosteroid-refractory graft-versus-host disease treated with ruxolitinib

상세보기
Biol Blood Marrow Transplant Harris 22 1 4 2016 10.1016/j.bbmt.2015.09.001 International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium

상세보기
Biol Blood Marrow Transplant Martin 15 7 777 2009 10.1016/j.bbmt.2009.03.012 Endpoints for clinical trials testing treatment of acute graft-versus-host disease: a joint statement

상세보기
Center for International Blood & Marrow Transplant Research (CIBMTR) . Clinical trial endpoints for patients with acute GVHD. https://www.cibmtr.org/Meetings/Materials/GVHDworkshop/pages/index.aspx. Accessed 1 February 2019.
Biol Blood Marrow Transplant Jagasia 21 3 389 2015 10.1016/j.bbmt.2014.12.001 National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report

상세보기
Biol Blood Marrow Transplant Jagasia 19 7 1129 2013 10.1016/j.bbmt.2013.04.018 Extracorporeal photopheresis versus anticytokine therapy as a second-line treatment for steroid-refractory acute GVHD: a multicenter comparative analysis

상세보기
Blood Socie 129 5 643 2017 10.1182/blood-2016-09-738625 A phase 3 randomized trial comparing inolimomab vs usual care in steroid-resistant acute GVHD

상세보기
Blood Magenau 131 12 1372 2018 10.1182/blood-2017-11-815746 α1-Antitrypsin infusion for treatment of steroid-resistant acute graft-versus-host disease

상세보기
Biol Blood Marrow Transplant Pidala 15 9 1116 2009 10.1016/j.bbmt.2009.05.019 Infliximab for managing steroid-refractory acute graft-versus-host disease

상세보기
Blood Chen 129 24 3256 2017 10.1182/blood-2017-03-772210 Phase 1 multicenter trial of brentuximab vedotin for steroid-refractory acute graft-versus-host disease

상세보기
Transfus Med Hemother Elgaz 46 1 27 2019 10.1159/000496809 Clinical use of mesenchymal stromal cells in the treatment of acute graft-versus-host disease

상세보기
Bone Marrow Transplant Garcia-Cadenas 52 1 107 2017 10.1038/bmt.2016.225 Patterns of infection and infection-related mortality in patients with steroid-refractory acute graft versus host disease

상세보기
Am J Hematol Polverelli 92 1 37 2017 10.1002/ajh.24572 Risk factors for infections in myelofibrosis: role of disease status and treatment. A multicenter study of 507 patients

상세보기
N Engl J Med Marty 377 25 2433 2017 10.1056/NEJMoa1706640 Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation

상세보기
Blood Major-Monfried 131 25 2846 2018 10.1182/blood-2018-01-822957 MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD

상세보기
Biol Blood Marrow Transplant Fløisand 25 4 720 2019 10.1016/j.bbmt.2018.11.013 Safety and effectiveness of vedolizumab in patients with steroid-refractory gastrointestinal acute graft-versus-host disease: a retrospective record review

상세보기
Biol Blood Marrow Transplant Kebriaei A phase 3 randomized study of remestemcel-L versus placebo added to second-line therapy in patients with steroid-refractory acute graft-versus-host disease [published online ahead of print 7 September 2019]

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Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH1): a multicenter, open-label phase 2 trial 원문보기

Abstract ▼ AI-Helper

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