TY - JOUR
T1 - Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis
AU - The BMT CTN 1703 Investigators
AU - Bolaños-Meade, Javier
AU - Hamadani, Mehdi
AU - Wu, Juan
AU - Al Malki, Monzr M.
AU - Martens, Michael J.
AU - Runaas, Lyndsey
AU - Elmariah, Hany
AU - Rezvani, Andrew R.
AU - Gooptu, Mahasweta
AU - Larkin, Karilyn T.
AU - Shaffer, Brian C.
AU - El Jurdi, Najla
AU - Loren, Alison W.
AU - Solh, Melhem
AU - Hall, Aric C.
AU - Alousi, Amin M.
AU - Jamy, Omer H.
AU - Perales, Miguel Angel
AU - Yao, Janny M.
AU - Applegate, Kristy
AU - Bhatt, Ami S.
AU - Kean, Leslie S.
AU - Efebera, Yvonne A.
AU - Reshef, Ran
AU - Clark, William
AU - Difronzo, Nancy L.
AU - Leifer, Eric
AU - Horowitz, Mary M.
AU - Jones, Richard J.
AU - Holtan, Shernan G.
N1 - Publisher Copyright:
© 2023 Massachusetts Medical Society.
PY - 2023
Y1 - 2023
N2 - 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 HLA-A, HLA-B, HLA-C, and HLA-DRB1 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.
AB - 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 HLA-A, HLA-B, HLA-C, and HLA-DRB1 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.
KW - Bone Marrow Transplantation
KW - Hematology/Oncology
KW - Leukemia/Lymphoma
KW - Treatments in Oncology
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U2 - 10.1056/NEJMoa2215943
DO - 10.1056/NEJMoa2215943
M3 - Article
C2 - 37342922
AN - SCOPUS:85164529275
SN - 0028-4793
VL - 388
SP - 2338
EP - 2348
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 25
ER -