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

Joseph Pidala, Mehdi Hamadani, Peter Dawson, Michael Martens, Amin M. Alousi, Madan Jagasia, Yvonne A. Efebera, Saurabh Chhabra, Iskra Pusic, Shernan G. Holtan, James L. M. Ferrara, John E. Levine, Marco Mielcarek, Claudio Anasetti, Joseph H. Antin, Javier Bolaños-meade, Alan Howard, Brent R. Logan, Eric S. Leifer, Theresa S. PritchardMary M. Horowitz, Margaret L. Macmillan

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)97-107
Number of pages11
Issue number2
StatePublished - Jan 9 2020

Bibliographical note

Funding Information:
The Blood and Marrow Transplant Clinical Trials Network is supported in part by grants #U10HL069294 and #U24HL138660 from the National Heart, Lung, and Blood Institute and the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors also acknowledge Center for International Blood and Marrow Transplantation Research support from Amgen, Magenta, Gamida Cell, and Medac.

Funding Information:
Conflict-of-interest disclosure: M.H. received research funding from Takeda, Otsuka, Spectrum, Astellas, and Incyte, and served on the advisory board of Pharmacyclics. M.J. served on the advisory board for and had a consultancy with Incyte; received research funding from Mallinckrodt and Janssen; had a consultancy with Kadmon: and served on the advisory board for Incyte. Y.A.E. received research funding from Celgene; served on the speaker’s bureau for Janssen and Akcea, and served on the independent review committee and speaker’s bureau for Takeda. S.G.H. served on the advisory board for Incyte and BMS. J.L.M.F. had a consultancy and intellectual property rights with Viracor and a

Funding Information:
consultancy with Xenikos. J.E.L. has royalties and intellectual property rights with Viracor and a consultancy with Therakos, Novartis, Ironwood, Incyte, and Bluebird. M.M.H. receives research funding from Celgene and Novartis. The remaining authors declare no competing financial interests.

Publisher Copyright:
© 2020 American Society of Hematology. All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Clinical Trial, Phase II
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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