Antithymocyte Globulin Reduces Need for Immunosuppressants After Hematopoietic Cell Transplantation From Unrelated Donors
In a phase III trial reported in The Lancet Oncology, Walker et al found that treatment with antithymocyte globulin reduced the need for immunosuppressive therapy in patients with hematologic malignancies receiving hematopoietic cell transplantation from unrelated donors.
Study Details
In this open-label trial, 196 evaluable patients aged 16 to 70 years from 10 centers in Canada and 1 in Australia who received myeloablative or nonmyeloablative or reduced-intensity conditioning regimens were randomized between June 2010 and July 2013 to receive antithymocyte globulin (n = 99) or no antithymocyte globulin (n = 97). Antithymocyte globulin was given at 0.5 mg/kg 2 days before, 2.0 mg/kg 1 day before, and 2.0 mg/kg 1 day after transplantation. All patients received graft-vs-host disease prophylaxis, including either cyclosporine or tacrolimus plus methotrexate or mycophenolate. The primary endpoint was freedom from all systemic immunosuppressive drugs without resumption up to 12 months after transplantation.
The antithymocyte globulin and no antithymocyte globulin groups were generally balanced for disease (chronic myeloid leukemia in 7% and 5%, acute myeloid leukemia in 39% and 40%, acute lymphocytic leukemia in 13% and 17%, myelodysplastic syndrome in 11% and 12%, chronic lymphocytic leukemia in 8% in both, lymphoma in 14% and 13%); in addition, the were balanced for disease stage (early in 58% and 61%), preparative regimen (myeloablative in 67% and 68%), full HLA match (84% and 81%), and graft cell type (blood in 89% and 88%).
Reduced Need for Immunosuppressants
At 12 months, 37% of patients in the antithymocyte globulin group vs 16% in the no antithymocyte globulin group were free from immunosuppressive treatment (adjusted odds ratio = 4.25, P = .00060). At 12 months, there were no differences between the groups in the rate of nonrelapse mortality (23% and 24%), disease relapse (11% and 16%), or all-cause mortality (25% and 35%). The antithymocyte globulin group had lower rates of acute graft-vs-host disease at 30 days (22% vs 37%) and at 100 days (50% vs 65%; P = .012 for trend) and chronic graft-vs-host disease at 12 months (22% vs 33%; P = .065 for trend).
Adverse Events
Serious adverse events occurred in 34% vs 42% of patients, and serious infection occurred in 42% and 38%. Epstein-Barr virus reactivation was observed in 20 antithymocyte globulin patients vs 2 no antithymocyte globulin patients; 2 of the participating centers, accounting for 20% of study patients, did not screen for Epstein-Barr virus reactivation. One patient in the antithymocyte globulin group died of Epstein-Barr virus reactivation.
The investigators concluded: “Antithymocyte globulin should be added to myeloblative and nonmyeloblative preparative regimens for haemopoietic cell transplantation when using unrelated donors. The benefits of decreases in steroid use are clinically significant. Epstein-Barr virus reactivation is increased but is manageable by prospective monitoring and the use of rituximab. Future trials could determine whether the doses of antithymocyte globulin used in this trial are optimum and could also provide additional evidence of a low relapse rate after nonmyeloablative regimens.”
The study was funded by the Canadian Institutes of Health Research and Sanofi.
Irwin Walker, MBBS, of McMaster University and Juravinski Hospital and Cancer Centre, is the corresponding author of The Lancet Oncology article.
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