In a phase II trial reported in the Journal of Clinical Oncology, Cutler et al found that early B-cell depletion with obinutuzumab reduced the risk of corticosteroid-requiring chronic graft-vs-host disease (GVHD) in allogeneic transplant recipients at increased risk of chronic GVHD.
Study Details
In the U.S. multicenter blinded trial, 178 transplant recipients who were receiving tacrolimus-based GVHD prophylaxis and were at higher risk of chronic GVHD were randomly assigned between November 2016 and January 2023 to receive four doses of obinutuzumab at 1,000 mg once daily on days 90, 180, 270, and 365 after transplantation (n = 90) or placebo (n = 88). Antibody responses against Y chromosome–encoded minor histocompatibility (H-Y) antigens were measured and correlated with the incidence of corticosteroid-requiring chronic GVHD. The primary endpoint was 1-year incidence of corticosteroid-requiring chronic GVHD.
Key Findings
The trial was halted early due to slow enrollment associated with the COVID-19 pandemic.
Prophylactic obinutuzumab was associated with ‘‘profound’’ B-cell depletion. The incidence of corticosteroid-requiring chronic GVHD at 1 year was 13.3% in the obinutuzumab group vs 35.2% in the placebo group (P = .0005). The obinutuzumab group exhibited a significant improvement in immunosuppression-free relapse-free survival at 2 years (48% vs 34%, P = .02).
Among patients without preformed H-Y antibodies at the time of study intervention, patients in the obinutuzumab group had the most significant reduction in corticosteroid-requiring chronic GVHD at 12 months (8.6%) compared with patients in the obinutuzumab group with H-Y antibodies (40%) or placebo participants regardless of antibody status (41% with antibodies, 57% without antibodies).
Neutropenia was more common in the obinutuzumab group. No significant difference in nonrelapse mortality was observed.
The investigators concluded: “In allogeneic transplant recipients at higher risk of [chronic GVHD], early B-cell depletion results in a significant reduction in the incidence of corticosteroid-requiring [chronic GVHD].”
Corey Cutler, MD, of MPH Division of Transplantation and Cellular Therapy, Dana-Farber Cancer Institute, Boston, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
