Tacrolimus/sirolimus vs tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic HCT

• Published in: Blood Vol. 124; no. 8; pp. 1372 - 1377
• Main Authors: Cutler, Corey, Logan, Brent, Nakamura, Ryotaro, Johnston, Laura, Choi, Sung, Porter, David, Hogan, William J., Pasquini, Marcelo, MacMillan, Margaret L., Hsu, Jack W., Waller, Edmund K., Grupp, Stephan, McCarthy, Philip, Wu, Juan, Hu, Zhen-Huan, Carter, Shelly L., Horowitz, Mary M., Antin, Joseph H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21.08.2014; American Society of Hematology
• Subjects: Adolescent; Adult; Allografts; Disease-Free Survival; Female; Follow-Up Studies; Graft vs Host Disease - mortality; Graft vs Host Disease - prevention & control; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents - administration & dosage; Male; Methotrexate - administration & dosage; Middle Aged; Sirolimus - administration & dosage; Stomatitis - mortality; Stomatitis - prevention & control; Survival Rate; Tacrolimus - administration & dosage; Time Factors; Transplantation
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2014-04-567164

Grades 2-4 acute graft-versus-host disease (GVHD) occurs in approximately 35% of matched, related donor (MRD) allogeneic hematopoietic cell transplantation (HCT) recipients. We sought to determine if the combination of tacrolimus and sirolimus (Tac/Sir) was more effective than tacrolimus and methotrexate (Tac/Mtx) in preventing acute GVHD and early mortality after allogeneic MRD HCT in a phase 3, multicenter trial. The primary end point of the trial was to compare 114-day grades 2-4 acute GVHD-free survival using an intention-to-treat analysis of 304 randomized subjects. There was no difference in the probability of day 114 grades 2-4 acute GVHD-free survival (67% vs 62%, P = .38). Grades 2-4 GVHD was similar in the Tac/Sir and Tac/Mtx arms (26% vs 34%, P = .48). Neutrophil and platelet engraftment were more rapid in the Tac/Sir arm (14 vs 16 days, P < .001; 16 vs 19 days, P = .03). Oropharyngeal mucositis was less severe in the Tac/Sir arm (peak Oral Mucositis Assessment Scale score 0.70 vs 0.96, P < .001), but otherwise toxicity was similar. Chronic GVHD, relapse-free survival, and overall survival at 2 years were no different between study arms (53% vs 45%, P = .06; 53% vs 54%, P = .77; and 59% vs 63%, P = .36). Based on similar long-term outcomes, more rapid engraftment, and less oropharyngeal mucositis, the combination of Tac/Sir is an acceptable alternative to Tac/Mtx after MRD HCT. This study was funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; and the trial was registered at www.clinicaltrials.gov as #NCT00406393. •Tac/Sir prophylaxis provides equivalent GVHD-free survival when compared with Tac/Mtx in MRD transplantation.•Tac/Sir is associated with more rapid engraftment and reduced oropharyngeal mucositis after MRD transplantation.