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经典型霍奇金淋巴瘤 PD-1 阻断后行同种异体移植。

Allogeneic transplantation after PD-1 blockade for classic Hodgkin lymphoma.

机构信息

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Department of Oncology and Hematology, Humanitas Clinical and Research Center-IRCCS, Rozzano-Milano, Italy.

出版信息

Leukemia. 2021 Sep;35(9):2672-2683. doi: 10.1038/s41375-021-01193-6. Epub 2021 Mar 3.

Abstract

Anti-PD-1 monoclonal antibodies yield high response rates in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but most patients will eventually progress. Allogeneic hematopoietic cell transplantation (alloHCT) after PD-1 blockade may be associated with increased toxicity, raising challenging questions about the role, timing, and optimal method of transplantation in this setting. To address these questions, we assembled a retrospective cohort of 209 cHL patients who underwent alloHCT after PD-1 blockade. With a median follow-up among survivors of 24 months, the 2-year cumulative incidences (CIs) of non-relapse mortality and relapse were 14 and 18%, respectively; the 2-year graft-versus-host disease (GVHD) and relapse-free survival (GRFS), progression-free survival (PFS), and overall survival were 47%, 69%, and 82%, respectively. The 180-day CI of grade 3-4 acute GVHD was 15%, while the 2-year CI of chronic GVHD was 34%. In multivariable analyses, a longer interval from PD-1 to alloHCT was associated with less frequent severe acute GVHD, while additional treatment between PD-1 and alloHCT was associated with a higher risk of relapse. Notably, post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis was associated with significant improvements in PFS and GRFS. While awaiting prospective clinical trials, PTCy-based GVHD prophylaxis may be considered the optimal transplantation strategy for this patient population.

摘要

抗 PD-1 单克隆抗体在复发/难治性经典霍奇金淋巴瘤 (cHL) 患者中产生了很高的反应率,但大多数患者最终会进展。PD-1 阻断后进行同种异体造血细胞移植 (alloHCT) 可能与毒性增加有关,这对该情况下移植的作用、时机和最佳方法提出了具有挑战性的问题。为了解决这些问题,我们汇集了 209 例接受 PD-1 阻断后 alloHCT 的 cHL 患者的回顾性队列。在幸存者中,中位随访时间为 24 个月,2 年非复发死亡率和复发的累积发生率 (CI) 分别为 14%和 18%;2 年移植物抗宿主病 (GVHD) 和无复发存活率 (GRFS)、无进展生存率 (PFS) 和总生存率分别为 47%、69%和 82%。3-4 级急性 GVHD 的 180 天 CI 为 15%,而慢性 GVHD 的 2 年 CI 为 34%。多变量分析表明,PD-1 至 alloHCT 的间隔时间较长与严重急性 GVHD 的发生频率较低相关,而 PD-1 与 alloHCT 之间的额外治疗与更高的复发风险相关。值得注意的是,移植后环磷酰胺 (PTCy) 为基础的 GVHD 预防与 PFS 和 GRFS 的显著改善相关。在等待前瞻性临床试验的同时,PTCy 为基础的 GVHD 预防可能被认为是该患者群体的最佳移植策略。

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