Randomized, Placebo-Controlled Trial of B-Cell Depletion for Prevention of Corticosteroid-Requiring Chronic Graft-Versus-Host Disease.

As B-cell-directed therapy can effectively treat established cGVHD, we tested whether prophylactic B-cell depletion could prevent the development of corticosteroid-requiring cGVHD following allogeneic transplantation.

由于B细胞靶向治疗可以有效治疗已建立的cGVHD，我们测试了预防性B细胞耗竭是否可以预防异基因移植后需要皮质类固醇的cGVHD的发展。

Methods

We performed a randomized, placebo-controlled, and blinded trial comparing four doses of the B-cell-depleting antibody obinutuzumab (1,000 mg once on days 90, 180, 270, and 365 after transplantation) with placebo in transplant recipients receiving tacrolimus-based GVHD prevention at higher risk of cGVHD.

我们开展了一项随机、安慰剂对照且设盲的试验，比较了四种剂量的B细胞耗竭抗体奥布珠单抗（移植后第90、180、270和365天各一次，每次1,000毫克）与安慰剂在接受他克莫司为基础的GVHD预防治疗的移植受者中的效果，这些受者有较高的慢性移植物抗宿主病（cGVHD）风险。

The primary end point was the 1-year incidenceof corticosteroid-requiring cGVHD.

主要终点是1年内需要皮质类固醇治疗的cGVHD发生率。

We measured antibody responses against Y chromosome-encoded minor histocompatibility (H-Y) antigens and correlated their occurrence with corticosteroid-requiring cGVHD incidence.

我们测量了针对Y染色体编码的次要组织相容性（H-Y）抗原的抗体反应，并将它们的发生与需要皮质类固醇的慢性移植物抗宿主病（cGVHD）的发病率相关联。

Results

One hundred seventy-eight participants were analyzed.

分析了178名参与者。

The prophylactic administration of obinutuzumab resulted in profound B-cell depletion, a significant reduction in the incidenceof steroid-requiring cGVHD at 1 year (13.3% v 35.2%; P = .0005), and an improvement in immunosuppression-free, relapse-free survival (48% v 34% at 2 years; P = .02).

预防性使用奥布珠单抗导致了显著的B细胞耗竭，1年内需要类固醇治疗的慢性移植物抗宿主病（cGVHD）发生率显著降低（13.3%对比35.2%；P = .0005），并且在无免疫抑制治疗、无复发生存方面有所改善（2年时为48%对比34%；P = .02）。

Neutropenia was more common in the obinutuzumab arm, but nonrelapse mortality was not different.

在奥布珠单抗组中，中性粒细胞减少更为常见，但非复发死亡率并无差异。

In participants without preformed H-Y antibodies at the time of study intervention, obinutuzumab resulted in the most significant reduction in steroid-requiring cGVHD at 12 months (8.6%) compared with obinutuzumab participants with H-Y antibodies (40%) or placebo participants regardless of antibody status (41% with antibodies, 57% without antibodies).

在研究干预时没有预先形成H-Y抗体的参与者中，奥布替组单抗在12个月时导致需要类固醇的cGVHD显著减少（8.6％），与有H-Y抗体的奥布替组单抗参与者（40％）或无论抗体状态的安慰剂参与者（有抗体41％，无抗体57％）相比。

Conclusions

In allogeneic transplant recipients at higher risk of cGVHD, early B-cell depletion results in a significant reduction in the incidenceof corticosteroid-requiring cGVHD.

对于cGVHD高风险的异基因移植受者，早期B细胞耗竭导致需要类固醇的cGVHD发生率显著降低。