단일 기관 내 Steroid-Refractory Graft-versus-Host Disease 환자에서의 Ruxolitinib 반응성 평가
Evaluation of Ruxolitinib for Steroid-Refractory Graft-versus-Host Disease in Hospital
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background : Graft-versus-host disease (GVHD) is a complication reported in 30–50% of patients who receive homologous hematopoietic stem cell transplantation. Although systemic corticosteroids are recommended as primary treatment, approximately 50% develop steroid-refractory GVHD (SR-GVHD) with high mortality. In May 2022, ruxolitinib was approved by the Ministry of Food and Drug Safety for the treatment of SR-GVHD, but there is limited data on treatment responses in Korean patients. The purpose of this study was to evaluate the effectiveness of ruxolitinib in patients with SR-GVHD. Methods : We enrolled patients with GVHD who had received ruxolitinib treatement at Severance Hospital between January 2017 to July 2022. We evaluated the overall response rate (ORR) and non-relapse mortality (NRM) at the time of ruxolitinib discontinuation. Patients and GVHD characteristics were analyzed according to the responder and non-responder groups of ruxolitinib, and the steroid-sparing effect was estimated based on whether the co-administered steroids were reduced. Results : There were no significant differences in baseline patient characteristics and GVHD characteristics between the responder and non-responder groups. The overall responsive rate (ORR) for ruxolitinib was 50% (22 of 44 patients). During the administration of ruxolitinib, 91% of responders and 46% of non-responders experienced a reduction of steroid dose reduction (p<0.01). The NRM was 10% in the responder group and 64% in the non-responder group (p<0.01), and the main cause of death was infection. Conclusion : The results demonstrate that ruxolitinib has a steroid-sparing effect in patients with SR-GVHD, as evidenced by the higher number of patients who experienced steroid dose reduction and the lower NRM in responders than non-responders. This suggests the possibility of reducing steroid-induced infection risk and mortality.
Abstract
Background : Graft-versus-host disease (GVHD) is a complication reported in 30–50% of patients who receive homologous hematopoietic stem cell transplantation. Although systemic corticosteroids are recommended as primary treatment, approximately 50% develop steroid-refractory GVHD (SR-GVHD) with high mortality. In May 2022, ruxolitinib was approved by the Ministry of Food and Drug Safety for the treatment of SR-GVHD, but there is limited data on treatment responses in Korean patients. The purpose of this study was to evaluate the effectiveness of ruxolitinib in patients with SR-GVHD. Methods : We enrolled patients with GVHD who had received ruxolitinib treatement at Severance Hospital between January 2017 to July 2022. We evaluated the overall response rate (ORR) and non-relapse mortality (NRM) at the time of ruxolitinib discontinuation. Patients and GVHD characteristics were analyzed according to the responder and non-responder groups of ruxolitinib, and the steroid-sparing effect was estimated based on whether the co-administered steroids were reduced. Results : There were no significant differences in baseline patient characteristics and GVHD characteristics between the responder and non-responder groups. The overall responsive rate (ORR) for ruxolitinib was 50% (22 of 44 patients). During the administration of ruxolitinib, 91% of responders and 46% of non-responders experienced a reduction of steroid dose reduction (p<0.01). The NRM was 10% in the responder group and 64% in the non-responder group (p<0.01), and the main cause of death was infection. Conclusion : The results demonstrate that ruxolitinib has a steroid-sparing effect in patients with SR-GVHD, as evidenced by the higher number of patients who experienced steroid dose reduction and the lower NRM in responders than non-responders. This suggests the possibility of reducing steroid-induced infection risk and mortality.
참고문헌 (20)
- Kitko C, "National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IIa. The 2020 Clinical Implementation and Early Diagnosis Working Group Report", Transplantation and Cellular Therapy, 27(7), pp.545~557 (2021)
- Jacobsohn DA, "Acute graft versus host disease", Orphanet J Rare Dis (2007)[DOI]
- Pidala J, "Patient-reported quality of life is associated with severity of chronic graft-versushost disease as measured by NIH criteria:report on baseline data from the Chronic GVHD Consortium", Blood, 117(17), pp.4651~4657 (2011)
- Lee SJ, "Quality of life associated with acute and chronic graft-versus-host disease", Bone Marrow Transplant, 38(4), pp.305~310 (2006)
- Pidala J, "Glucocorticoid-refractory acute graft-versus-host disease", Biol Blood Marrow Transplant, 16, pp.1504~1518 (2010)
- Zeiser R, "Acute graft-versushost disease – biologic process, prevention, and therapy", N Engl J Med, 377(22), pp.2167~2179 (2017)
- 한혜영, "소아에서 스테로이드 저항성 이식편대숙주병에 대한 Etanercept의 효과", Blood Research, 44(4), pp.212~219 (2009), 대한혈액학회
- Zeiser R, "Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease", N Engl J Med, 385(3), pp.228~238 (2021)
- Schroeder MA, "The Role of Janus Kinase Signaling in Graft-Versus-Host Disease and Graft Versus Leukemia", Biol Blood Marrow Transplant, 24(6), pp.1125~1134 (2018)
- Zeiser R, "Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease", N Eng J Med, 382(19), pp.1800~1810 (2020)
- "FDA approves ruxolitinib for chronic graftversus-host disease"[URL]
- "FDA approves ruxolitinib for acute graftversus-host disease"[URL]
- "Annual the number of BMT in Korea"[URL]
- Wu H, "Evaluation of Ruxolitinib for Steroid-Refractory Chronic Graft-vs-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation", JAMA Netw Open, 4(1), pp.e2034750~ (2021)
- Escamilla Gómez V, "Ruxolitinib in refractory acute and chronic graft-versus-host disease: a multicenter survey study", Bone Marrow Transplant, 55(3), pp.641~648 (2020)
- Harris AC, "International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium", Biol Blood Marrow Transplant, 22(1), pp.4~10 (2016)
- Lee SJ, "Measuring therapeutic response in chronic graft-versus-host disease. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease:IV. The 2014 Response Criteria Working Group report", Biol Blood Marrow Transplant, 21(6), pp.984~999 (2015)
- Yuan S, "Ruxolitinib for Steroid-Refractory Acute Graft-Versus-Host Disease: A Single Centre Retrospective Study", Blood, 138(Supplement 1), pp.4878~ (2021)
- Jagasia M, "Ruxolitinib for the treatment of steroid-refractory acute GVHD (REACH 1): a multicenter, open-label phase 2trial", Blood, 135(20), pp.1739~1749 (2020)
- Abedin S, "Efficacy, Toxicity, and Infectious Complications in Ruxolitinib-Treated Patients with Corticosteroid-Refractory Graft-versus-Host Disease after Hematopoietic Cell Transplantation", Biol Blood Marrow Transplant, 25(8), pp.1689~1694 (2019)