In the phase III BMT CTN 1703 trial reported in The New England Journal of Medicine, Bolaños‑Meade et al found that posttransplantation cyclophosphamide-based graft-vs-host disease (GVHD) prophylaxis improved GVHD-free, relapse-free survival vs standard prophylaxis in patients with hematologic cancers undergoing allogeneic hematopoietic stem cell transplantation (HSCT).
Study Details
In the U.S. multicenter trial, 431 patients were randomly assigned between June 2019 and June 2021 to receive posttransplantation prophylaxis with cyclophosphamide, tacrolimus, and mycophenolate mofetil (n = 214) or standard tacrolimus/methotrexate prophylaxis. Patients underwent HSCT from a human leukocyte antigen (HLA)-matched related donor or an 8/8 or 7/8 matched unrelated donor after reduced-intensity conditioning.
The primary endpoint was GVHD-free, relapse-free survival at 1 year in the intent-to-treat population, with events defined as grade III or IV acute GVHD, chronic GVHD requiring systemic immunosuppression, disease relapse or progression, and any-cause death.
Key Findings
At 1 year, adjusted GVHD-free, relapse-free survival was 52.7% (95% confidence interval [CI] = 45.8%–59.2%) in the cyclophosphamide-based treatment group vs 34.9% (95% CI = 28.6%–41.3%) in the standard treatment group. On multivariate analysis, the hazard ratio (HR) favoring the cyclophosphamide-based group was 0.64 (95% CI = 0.49–0.83, P = .001).
The cyclophosphamide-based group had lower 1-year cumulative incidence of grade III or IV acute GVHD (6.3% vs 14.7%) and 1-year cumulative incidence of chronic GVHD (21.9% vs 35.1%), as well as greater immunosuppression-free survival at 1 year (50.0% vs 39.7%).
No substantial differences between the cyclophosphamide-based group vs the standard group were observed in 1-year rates of overall survival (77.0% vs 72.2%), disease-free survival (67.0% vs 62.4%), disease relapse or progression (20.8% vs 20.2%), or transplantation-related death (12.3% vs 17.2%). The cumulative incidence of neutrophil recovery at day 28 was 90.3% vs 93.4%, and cumulative incidence of platelet recovery at day 100 was 90.3% vs 92.8%.
The investigators concluded, “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.”
Javier Bolaños‑Meade, MD, of Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by the National Heart, Lung, and Blood Institute and others. For full disclosures of the study authors, visit nejm.org.
