Department of Medicine, Houston Methodist Hospital, Houston, TX.
Division of Biostatistics, Washington University in St. Louis, St. Louis, MO.
Transplantation. 2024 Mar 1;108(3):777-786. doi: 10.1097/TP.0000000000004841. Epub 2024 Feb 20.
Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.
We conducted a pilot randomized controlled trial (RCT) at 2 sites to assess the feasibility and inform the design of a large-scale RCT. All participants were treated with rabbit antithymocyte globulin for induction immunosuppression. Participants in the control arm were treated with tacrolimus, mycophenolate mofetil, and prednisone, and participants in the belatacept arm were treated with tacrolimus, belatacept, and prednisone through day 89 after transplant then converted to belatacept, mycophenolate mofetil, and prednisone for the remainder of year 1.
After randomizing 27 participants, 3 in the belatacept arm died compared with none in the control arm. As a result, we stopped enrollment and treatment with belatacept, and all participants were treated with standard-of-care immunosuppression. Overall, 6 participants in the belatacept arm died compared with none in the control arm (log rank P = 0.008). We did not observe any differences in the incidence of DSA, acute cellular rejection, antibody-mediated rejection, CLAD, or infections between the 2 groups.
We conclude that the investigational regimen used in this pilot RCT is associated with increased mortality after lung transplantation.
慢性肺移植物功能障碍（CLAD）是肺移植后第一年以后死亡的主要原因。供体特异性抗体（DSA）的发展是 CLAD 的一个公认的危险因素。基于肾移植的经验，我们假设选择性 T 细胞共刺激阻断剂贝利尤单抗可降低肺移植后 DSA 的发生率，从而降低 CLAD 的风险。
我们在 2 个地点进行了一项先导性随机对照试验（RCT），以评估其可行性并为大规模 RCT 设计提供信息。所有参与者均接受兔抗胸腺细胞球蛋白进行诱导免疫抑制。对照组参与者接受他克莫司、霉酚酸酯和泼尼松治疗，贝利尤单抗组参与者接受他克莫司、贝利尤单抗和泼尼松治疗，直至移植后第 89 天，然后转换为贝利尤单抗、霉酚酸酯和泼尼松，用于第 1 年的剩余时间。
在随机分配 27 名参与者后，贝利尤单抗组有 3 名参与者死亡，而对照组没有参与者死亡。因此，我们停止了贝利尤单抗的入组和治疗，所有参与者均接受标准免疫抑制治疗。总的来说，贝利尤单抗组有 6 名参与者死亡，而对照组没有参与者死亡（对数秩 P = 0.008）。我们没有观察到两组之间 DSA、急性细胞排斥、抗体介导的排斥、CLAD 或感染的发生率有任何差异。
我们得出结论，这项先导性 RCT 中使用的研究方案与肺移植后死亡率的增加有关。
