• Javier Bolaños-Meade, Mehdi Hamadani, Juan Wu, Monzr M Al Malki, Michael J Martens, Lyndsey Runaas, Hany Elmariah, Andrew R Rezvani, Mahasweta Gooptu, Karilyn T Larkin, Brian C Shaffer, Najla El Jurdi, Alison W Loren, Melhem Solh, Aric C Hall, Amin M Alousi, Omer H Jamy, Miguel-Angel Perales, Janny M Yao, Kristy Applegate, Ami S Bhatt, Leslie S Kean, Yvonne A Efebera, Ran Reshef, William Clark, Nancy L DiFronzo, Eric Leifer, Mary M Horowitz, Richard J Jones, Shernan G Holtan, and BMT CTN 1703 Investigators.
• From the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, and the Department of Oncology, Johns Hopkins University School of Medicine, Baltimore (J.B.-M., R.J.J.), Emmes, Rockville (J.W., K.A.), and the Division of Blood Diseases and Resources (N.L.D.) and the Office of Biostatistics Research (E.L.), National Heart, Lung, and Blood Institute, Bethesda - all in Maryland; the Blood and Marrow Transplant Program and Cellular Therapy Program (M.H.) and the Center for International Blood and Marrow Transplant Research (CIBMTR), Department of Medicine (M.H., M.M.H.), the CIBMTR Division of Biostatistics, Institute for Health and Equity (M.J.M.), and the Division of Hematology and Oncology, Department of Medicine (L.R.), Medical College of Wisconsin, Milwaukee, and the Division of Hematology and Oncology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison (A.C.H.) - both in Wisconsin; the Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford (A.R.R.), the Department of Hematology and Hematopoietic Cell Transplantation, City of Hope (M.M.A.M.), and the Department of Pharmacy, City of Hope National Medical Center (J.M.Y.), Duarte, and the Division of Hematology, Departments of Medicine and Genetics, Stanford University, Palo Alto (A.S.B.) - all in California; the Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer and Research Institute, Tampa, FL (H.E.); the Department of Hematology and Oncology, Dana-Farber Cancer Institute (M.G., L.S.K.), and the Department of Pediatrics, Harvard Medical School, and the Division of Pediatric Hematology and Oncology, Boston Children's Hospital (L.S.K.) - all in Boston; the Ohio State University Comprehensive Cancer Center, Columbus (K.T.L., Y.A.E.); Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, and the Department of Medicine, Weill Cornell Medical College (B.C.S., M.-A.P.), and the Blood and Marrow Transplantation Program, Columbia University Irving Medical Center (R.R.) - all in New York; the Division of Hematology, Oncology, and Transplantation, University of Minnesota, Minneapolis (N.E.J., S.G.H.); the Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia (A.W.L.); the Blood and Marrow Transplant Program at Northside Hospital, Atlanta (M.S.); the Department of Stem Cell Transplantation and Cellular Therapy, the University of Texas M.D. Anderson Cancer Center, Houston (A.M.A.); the Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham (O.H.J.); and the Division of Hematology-Oncology and Palliative Care, Department of Medicine, Virginia Commonwealth University, Richmond (W.C.).
• N. Engl. J. Med. 2023 Jun 22; 388 (25): 233823482338-2348.

BackgroundIn 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.MethodsIn 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.ResultsIn 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.ConclusionsAmong 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 ClinicalTrials.gov number, NCT03959241.).Copyright © 2023 Massachusetts Medical Society.

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