The outcomes of a phase II Blood and Marrow Transplant Clinical Trials Network (BMT CTN) prospective, randomized trial (BMT CTN 1203) showed promising results for a new preventive regimen for graft-versus-host-disease (GVHD). Researchers found that tacrolimus, mycophenolate mofetil, with post-hematopoietic cell transplant (HCT) cyclophosphamide (TMMPT-Cy) produced the best GVHD-free, relapse-free survival (GRFS) for patients who received an allogeneic HCT when compared to the current standard of care.
The researchers tested three prophylactic regimens for GVHD comparing each to a non-randomized control group receiving the current standard of care, methotrexate and calcineurin inhibitor, to assess the incidence of GRFS. GRFS was defined as time from transplant to onset of grade III-IV acute GVHD, chronic GVHD requiring systemic immunosuppression, disease relapse or death.
The study included 273 patients aged 18 to 75 years who were randomly assigned (1:1:1) into block sizes to receive TMMPT-Cy; tacrolimus, methotrexate and bortezomib; or tacrolimus, methotrexate and maraviroc.
Of the three protocols, TMMPT-Cy was the only intervention to show better GRFS results (hazard ratio: 0.72, 90% confidence index 0.54-0.94, p=0.044) with comparable relapse and survival when compared to the control group receiving the standard of care combination.
According to the researchers, this is the first randomized clinical trial to show promising outcomes with a high-dose post-HCT cyclophosphamide-based regimen versus the current standard of care for GVHD prophylaxis. A phase III trial (BMT CTN 1703) will prospectively compare TMMPT-Cy to tacrolimus and methotrexate.
Bolaños-Meade J, et al., The Lancet Haematology