B-cell depletion for prevention of corticosteroid-requiring cGvHD after allo-HSCT: A phase II study

Results from a prospective, multicenter, randomized, placebo-controlled, blinded phase II study (NCT02867384), evaluating B-cell depletion with obinutuzumab for the prevention of corticosteroid-requiring chronic graft-versus-host disease (cGvHD) in higher-risk patients (N = 178) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), were published in the Journal of Clinical Oncology by Cutler et al. Patients received tacrolimus-based graft-versus-host disease (GvHD) prophylaxis, with obinutuzumab 1,000 mg (n = 90) or placebo (n = 88) administered on Days 90, 180, 270, and 365 (±10 days) after transplantation. The primary endpoint was the 1-year incidence of corticosteroid-requiring cGvHD.

Key data: At 1 year, corticosteroid-requiring cGvHD occurred in 13.3% vs 35.2% with obinutuzumab vs placebo, respectively (22% difference; 90% confidence interval [CI], 12–32; p = 0.0005). Two-year immunosuppression-free, relapse-free survival (IRFS) was higher with obinutuzumab vs placebo (48% vs 34%; p = 0.02), while relapse, non-relapse mortality (NRM), progression-free survival (PFS), and overall survival (OS) were similar between groups. Among male patients with evaluable samples (n = 87), 12-month corticosteroid-requiring cGvHD was lower with obinutuzumab in those with no/nonspecific H-Y antibodies (8.6%) and higher in those with preformed H-Y antibodies (40%). Grade 3–4 neutropenia was more common with obinutuzumab (37.5% vs 4.6%; p < 0.0001), but Grade ≥3 infection was similar (4.4% vs 3.4%; p = 1).

Key learning: Prophylactic B-cell depletion with obinutuzumab reduced corticosteroid-requiring cGvHD in higher-risk allo-HSCT recipients, with greatest benefit observed in patients without preformed H-Y antibodies, supporting earlier intervention in future trials.