Randomized, placebo-controlled trial of B-cell depletion for prevention of corticosteroid-requiring chronic graft-versus-host disease

Chronic graft-versus-host disease (cGVHD) is associated with abnormal B-cell biology and aberrant antibody responses. A randomized trial at Dana-Farber Cancer Institute (Boston, MA) tested whether prophylactic B-cell depletion could prevent the development of corticosteroid-requiring cGVHD following allogeneic transplantation. One hundred seventy-eight patients were randomized to receive the B-cell-depleting antibody obinutuzumab (1000 mg once on days 90, 180, 270, and 365 after transplantation) or placebo in transplant recipients receiving tacrolimus-based GVHD prevention at higher risk of cGVHD. The primary endpoint was 1-year incidence of corticosteroid-requiring cGVHD. The prophylactic administration resulted in profound B-cell depletion, a significant reduction in the incidence of steroid-requiring cGVHD at 1 year (13.3% versus 35.2%; p=0.0005) and improvement in immunosuppression-free, relapse-free survival (48% versus 34% at 2 years; p=0.02). Neutropenia was more common in the obinutuzumab arm, but nonrelapse mortality was not different. The authors conclude that in allogeneic transplant recipients at higher risk of cGVHD, early B-cell depletion resulted in a significant reduction in the incidence of corticosteroid-requiring cGVHD.