Study sets new standard for graft-versus-host disease prevention after stem cell transplant
Clinicians have a new standard for graft-versus-host disease (GVHD) prevention after allogeneic hematopoietic stem cell transplantation, according to results from a phase III study published June 22 in the New England Journal of Medicine. The new standard is more effective at preventing GVHD and came with less side effects, compared with the current gold standard.
The researchers say that for the first time since the 1980s, we have a more effective drug therapy to prevent severe cases of GVHD, and therefore, we have a new standard of care.
The current gold standard to prevent GVHD after bone marrow transplants is a combination of two drugs: a calcineurin inhibitor, such as tacrolimus or cyclosporine, and methotrexate. In the current phase III study, researchers from multiple institutions tested this standard to prevent GVHD against an experimental regimen of three drugs: cyclophosphamide, tacrolimus, and mycophenolate mofetil. Patients were recruited and randomized to either arm. This was done during the COVID-19 pandemic, but despite that, the study completed accrual ahead of time: 431 patients were enrolled from 37 centers across the United States. Patients were HLA matched to donors if related, and if unrelated, they were to be matched but could have one antigen mismatch. It took two years to enroll all patients (6/19 to 6/21) and patients were followed for at least one year.
Patients achieved the primary endpoint if they were alive, without acute GVHD grade III-IV, without chronic GVHD needing immunosuppression, and without relapse or progression from their cancer. At one year, the probability of achieving the endpoint was 52.7% for those getting the cyclophosphamide platform compared with 34.9% for those getting methotrexate and tacrolimus.
