Antithymocyte globulin reduces acute GVHD incidence after matched sibling donor transplant
Antithymocyte globulin decreased incidence of acute graft-versus-host-disease after allogeneic stem cell transplantation from an HLA-matched sibling donor, according to randomized study results published in Journal of Clinical Oncology.
The addition of antithymocyte globulin (ATG) to conventional GVHD prophylaxis conferred the benefit without impacting cumulative incidence of relapse or nonrelapse mortality, researchers noted.
“Allogeneic hematopoietic stem cell transplantation is the most effective method for curing a variety of hematologic malignancies, [and] GVHD is the main cause of morbidity and mortality after [these transplants],” Ying-Jun Chang, PhD, medical professional at Peking University People's Hospital in China, and colleagues wrote. “Because the response of acute GVHD to rst-line therapy is far from satisfactory and the long-term survival rate in patients with glucocorticoid-refractory acute GVHD is only 5% to 30%, prevention seems to be more important than treatment.”
The addition of cyclosporine to methotrexate prophylaxis has significantly reduced incidence of grade 2 to grade 4 acute GVHD since the 1980s. However, even with mycophenolate mofetil added to this combination, incidence remains as high as 30% after matched sibling donor transplants among patients aged 40 years and older.
Although ATG has been an important drug for prevention and treatment of acute GVHD, controversy exists regarding its benefit after HLA-matched sibling donor transplantation.
For that reason, Chang and colleagues analyzed the impact of ATG among 263 patients aged 40 to 60 years in China with standard-risk hematologic malignancies and an HLA-matched sibling donor. The researchers randomly assigned patients to GVHD prophylaxis with ATG dosed at 4.5 mg/kg in combination with cyclosporine, methotrexate and mycophenolate mofetil (n = 132) or the same regimen without ATG (n = 131).
Grade 2 to grade 4 acute GVHD on day 100 served as the primary endpoint.
Results showed a significantly reduced cumulative incidence rate of grade 2 to grade 4 acute GVHD in the ATG group compared with the control group (13.7% vs. 27%; P = .007).
Additionally, patients in the ATG group had significantly lower incidence of 2-year overall chronic GVHD (27.9% vs. 52.5%; P < .001) and 2-year extensive chronic GVHD (8.5% vs. 23.2%; P = .029) than the control group, as well as a significantly higher rate of 3-year GVHD RFS (38.7% vs. 24.5%; P = .003).
Researchers observed no differences between groups in cytomegalovirus reactivation, Epstein-Barr virus reactivation, 3-year nonrelapse mortality, 3-year cumulative incidence of relapse, 3-year OS and 3-year leukemia-free survival.
“To our knowledge, this study is the rst prospective [randomized controlled study] to demonstrate that ATG can effectively decrease acute GVHD after matched sibling donor transplantation in the cyclosporine era,” Chang and colleagues wrote. “This study also suggests that ATG should be included in transplantation regimens to further improve the prognosis of patients with hematologic malignancies after matched sibling donor transplantation.”
This approach does not represent the “holy grail” of disassociating GVHD from graft-versus-leukemia in allogeneic stem cell transplants, but it does help patients overall and will help clinicians move toward this goal, Nicolaus Kröger, MD, medical director of the department of stem cell transplantation at University Hospital Hamburg-Eppendorf in Germany, wrote in an accompanying editorial.
“From a patient’s perspective, having less acute and severe chronic GVHD and a better graft-versus-host/relapse-free survival after curative treatment should not be underestimated and is of exceptional value,” he wrote.