TY - JOUR
T1 - Randomized multicenter trial of sirolimus vs prednisone as initial therapy for standard-risk acute GVHD
T2 - The BMT CTN 1501 trial
AU - Pidala, Joseph
AU - Hamadani, Mehdi
AU - Dawson, Peter
AU - Martens, Michael
AU - Alousi, Amin M.
AU - Jagasia, Madan
AU - Efebera, Yvonne A.
AU - Chhabra, Saurabh
AU - Pusic, Iskra
AU - Holtan, Shernan G.
AU - Ferrara, James L.M.
AU - Levine, John E.
AU - Mielcarek, Marco
AU - Anasetti, Claudio
AU - Antin, Joseph H.
AU - Bolaños-Meade, Javier
AU - Howard, Alan
AU - Logan, Brent R.
AU - Leifer, Eric S.
AU - Pritchard, Theresa S.
AU - Horowitz, Mary M.
AU - MacMillan, Margaret L.
N1 - Publisher Copyright:
© 2020 American Society of Hematology. All rights reserved.
PY - 2020/1/9
Y1 - 2020/1/9
N2 - 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 5 58; prednisone, n 5 64). Others were AA3 (n 5 4), or AA status missing (n 5 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 www.clinicaltrials.gov as #NCT02806947.
AB - 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 5 58; prednisone, n 5 64). Others were AA3 (n 5 4), or AA status missing (n 5 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 www.clinicaltrials.gov as #NCT02806947.
UR - http://www.scopus.com/inward/record.url?scp=85077761109&partnerID=8YFLogxK
U2 - 10.1182/blood.2019003125
DO - 10.1182/blood.2019003125
M3 - Article
C2 - 31738834
AN - SCOPUS:85077761109
SN - 0006-4971
VL - 135
SP - 97
EP - 107
JO - Blood
JF - Blood
IS - 2
ER -