The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD.
Blood Adv. 2018 Sep 11;2(17):2226-2229. doi: 10.1182/bloodadvances.2018019208.
Published reports suggest that immune checkpoint inhibitors (ICIs) before allogeneic blood or marrow transplantation (alloBMT) may increase the incidence of graft-versus-host disease (GvHD), immune-related adverse events, and nonrelapse mortality (NRM); this led to the US Food and Drug Administration issuing a "Warning and Precaution" regarding the potential for life-threatening immune-mediated complications associated with alloBMT after nivolumab and pembrolizumab. We retrospectively reviewed the outcomes of 14 consecutive patients who received ICIs as their final salvage therapy before T-cell-replete alloBMT using reduced-intensity conditioning. All patients received posttransplant cyclophosphamide (PTCy), which significantly limits severe GvHD, even in the mismatched-donor setting. There was no grade 3-4 acute GvHD (aGvHD), and all 6 cases of grade 2 aGvHD readily resolved with immunosuppression. No patient experienced veno-occlusive disease of the liver, other immune-related adverse events, chronic GvHD, or NRM. There have been 2 relapses (15-month median follow-up), with 12 of 14 patients remaining alive, well, and progression-free. The only death was a result of disease relapse. Although more experience is needed, our data suggest that concerns over immunologic complications associated with ICIs should not preclude allogeneic bone marrow transplantation with PTCy as GvHD prophylaxis.
已发表的报告表明，在异基因血液或骨髓移植（alloBMT）之前使用免疫检查点抑制剂（ICIs）可能会增加移植物抗宿主病（GvHD）、免疫相关不良事件和非复发死亡率（NRM）的发生率；这导致美国食品和药物管理局（FDA）发布了关于 nivolumab 和 pembrolizumab 后与 alloBMT 相关的危及生命的免疫介导并发症的潜在风险的“警告和预防”。我们回顾性分析了 14 例连续患者的结果，这些患者在接受 T 细胞丰富的 alloBMT 前接受了 ICIs 作为其最后的挽救治疗，使用了低强度预处理方案。所有患者均接受了移植后环磷酰胺（PTCy）治疗，即使在不匹配供体的情况下，也能显著限制严重 GvHD 的发生。没有 3-4 级急性移植物抗宿主病（aGvHD），所有 6 例 2 级 aGvHD 均通过免疫抑制得到了很好的缓解。没有患者发生肝静脉闭塞性疾病、其他免疫相关不良事件、慢性 GvHD 或 NRM。有 2 例复发（中位随访时间 15 个月），14 例患者中有 12 例存活、情况良好且无进展。唯一的死亡是由于疾病复发。尽管需要更多的经验，但我们的数据表明，与 ICIs 相关的免疫并发症的担忧不应排除使用 PTCy 预防 GvHD 的异基因骨髓移植。
