Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis Journal Article
| Authors: | Bolaños-Meade, J.; Hamadani, M.; Wu, J.; Al Malki, M. M.; Martens, M. J.; Runaas, L.; Elmariah, H.; Rezvani, A. R.; Gooptu, M.; Larkin, K. T.; Shaffer, B. C.; El Jurdi, N.; Loren, A. W.; Solh, M.; Hall, A. C.; Alousi, A. M.; Jamy, O. H.; Perales, M. A.; Yao, J. M.; Applegate, K.; Bhatt, A. S.; Kean, L. S.; Efebera, Y. A.; Reshef, R.; Clark, W.; Difronzo, N. L.; Leifer, E.; Horowitz, M. M.; Jones, R. J.; Holtan, S. G.; for the BMT CTN 1703 Investigators |
| Article Title: | Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis |
| Abstract: | 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. © 2023 Massachusetts Medical Society. |
| Keywords: | bone marrow transplantation; leukemia/lymphoma; hematology/oncology; treatments in oncology |
| Journal Title: | New England Journal of Medicine |
| Volume: | 388 |
| Issue: | 25 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2023-06-22 |
| Start Page: | 2338 |
| End Page: | 2348 |
| Language: | English |
| DOI: | 10.1056/NEJMoa2215943 |
| PROVIDER: | scopus |
| PUBMED: | 37342922 |
| PMCID: | PMC10575613 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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