Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis.

TitlePost-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis.
Publication TypeJournal Article
Year of Publication2023
AuthorsBolaños-Meade, J, Hamadani, M, Wu, J, Malki, MMAl, Martens, MJ, Runaas, L, Elmariah, H, Rezvani, AR, Gooptu, M, Larkin, KT, Shaffer, BC, Jurdi, NEl, Loren, AW, Solh, M, Hall, AC, Alousi, AM, Jamy, OH, Perales, M-A, Yao, JM, Applegate, K, Bhatt, AS, Kean, LS, Efebera, YA, Reshef, R, Clark, W, DiFronzo, NL, Leifer, E, Horowitz, MM, Jones, RJ, Holtan, SG
Corporate AuthorsBMT CTN 1703 Investigators
JournalN Engl J Med
Date Published2023 Jun 22
KeywordsAdult, Antineoplastic Combined Chemotherapy Protocols, Bronchiolitis Obliterans Syndrome, Cyclophosphamide, Graft vs Host Disease, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Methotrexate, Mycophenolic Acid, Neoplasm Recurrence, Local, Tacrolimus, Unrelated Donors

BACKGROUND: In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against graft-versus-host disease (GVHD). A phase 2 study indicated the potential superiority of a post-transplantation regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil.

METHODS: In a phase 3 trial, we randomly assigned adults with hematologic cancers in a 1:1 ratio to receive cyclophosphamide-tacrolimus-mycophenolate mofetil (experimental prophylaxis) or tacrolimus-methotrexate (standard prophylaxis). The patients underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched (i.e., mismatched at only one of the , , , and loci) unrelated donor, after reduced-intensity conditioning. The primary end point was GVHD-free, relapse-free survival at 1 year, assessed in a time-to-event analysis, with events defined as grade III or IV acute GVHD, chronic GVHD warranting systemic immunosuppression, disease relapse or progression, and death from any cause.

RESULTS: In a multivariate Cox regression analysis, GVHD-free, relapse-free survival was significantly more common among the 214 patients in the experimental-prophylaxis group than among the 217 patients in the standard-prophylaxis group (hazard ratio for grade III or IV acute GVHD, chronic GVHD, disease relapse or progression, or death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P = 0.001). At 1 year, the adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) with experimental prophylaxis and 34.9% (95% CI, 28.6 to 41.3) with standard prophylaxis. Patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall and disease-free survival, relapse, transplantation-related death, and engraftment did not differ substantially between the groups.

CONCLUSIONS: Among patients undergoing allogeneic HLA-matched HSCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common among those who received cyclophosphamide-tacrolimus-mycophenolate mofetil than among those who received tacrolimus-methotrexate. (Funded by the National Heart, Lung, and Blood Institute and others; BMT CTN 1703 number, NCT03959241.).

Alternate JournalN Engl J Med
PubMed ID37342922
Grant List#U10HL069294 / HL / NHLBI NIH HHS / United States
#U24HL138660 / CA / NCI NIH HHS / United States