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Blood. 2020 Jan 9;135(2):97-107. doi: 10.1182/blood.2019003125.

Randomized multicenter trial of sirolimus vs prednisone as initial therapy for standard-risk acute GVHD: the BMT CTN 1501 trial.

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Blood and Marrow Transplantation and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
BMT and Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, WI.
Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI.
Emmes Corporation, Rockville, MD.
Department of Stem Cell Transplant and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX.
Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Blood and Marrow Transplantation Program, The Ohio State University, Columbus, OH.
Medical Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO.
Blood and Marrow Transplant Program, Departments of Pediatrics and Medicine, University of Minnesota Medical School, Minneapolis, MN.
Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount Sinai, New York, NY.
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD; and.
Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, MD.


Clinical- and biomarker-based tools may identify a lower-risk acute graft-versus-host disease (GVHD) population amenable to novel, reduced-intensity treatments. Previous data suggest sirolimus may rival standard of care prednisone. We conducted a National Heart, Lung, and Blood Institute/National Cancer Institute-funded Blood and Marrow Transplant Clinical Trials Network multicenter, open-label, randomized phase 2 trial to estimate the difference in day 28 complete response (CR)/partial response (PR) rates for sirolimus vs prednisone as initial treatment of patients with standard risk (SR) acute GVHD as defined by the Minnesota (MN) GVHD Risk Score and Ann Arbor (AA1/2) biomarker status. A total of 127 MN-SR patients were randomized (1:1), and 122 were AA1/2 (sirolimus, n = 58; prednisone, n = 64). Others were AA3 (n = 4), or AA status missing (n = 1). The day 28 CR/PR rates were similar for sirolimus 64.8% (90% confidence interval [CI], 54.1%-75.5%) vs 73% (90% CI, 63.8%-82.2%) for prednisone. The day 28 rate of CR/PR with prednisone ≤0.25 mg/kg/day was significantly higher for sirolimus than prednisone (66.7% vs 31.7%; P < .001). No differences were detected in steroid-refractory acute GVHD, disease-free survival, relapse, nonrelapse mortality, or overall survival. Sirolimus was associated with reduced steroid exposure and hyperglycemia, reduced grade 2 to 3 infections, improvement in immune suppression discontinuation and patient-reported quality of life, and increased risk for thrombotic microangiopathy. For patients with clinical- and biomarker-based SR acute GVHD, sirolimus demonstrates similar overall initial treatment efficacy as prednisone. In addition, sirolimus therapy spares steroid exposure and allied toxicity, does not compromise long-term survival outcomes, and is associated with improved patient-reported quality of life. This trial was registered at as #NCT02806947.

[Available on 2021-01-09]

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