CD19-directed chimeric antigen receptor T cell (CART19) therapy is efficient and approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL). To increase durable antitumor response, we previously designed tandem CART19/20 cells and shown longer progression-free survival. However, a proportion of CART19/20-treated patients will finally progress and require salvage therapies. In this study, we analyzed data from five patients with relapsed/refractory DLBCL who had disease progression or relapse following CART19/20 therapy and then treated with PD-1-blocking antibodies as salvage therapy. Two of five patients acquired complete remissions after anti-PD-1 therapy, including one patient remained ongoing remission for more than 21 months. One patient achieved a partial remission, and the other two had progressive diseases. No ≥ grade 3 treatment-related adverse events or cytokine release syndrome was observed. Immunohistochemistry of tumor specimens revealed higher PD-1/PD-L1 expression in responsive patients with anti-PD-1 therapy as compared to that in non-responders. After anti-PD-1 treatment, circulating T cells were activated in responders, and no significant expansion of CART19/20 cells was detected. Our data suggest that PD-1 blockade therapy can be active in patients with relapsed/refractory DLBCL after failure of CAR T cell therapy who had PD-L1 expression in tumor cells and high PD-1 level in tumor-infiltrated T cells.

中文翻译：

---

抗 PD-1 抗体作为 CART19/20 治疗后进展/复发的弥漫性大 B 细胞淋巴瘤患者的挽救疗法

CD19 导向的嵌合抗原受体 T 细胞 (CART19) 疗法是有效的，并被批准用于复发/难治性弥漫性大 B 细胞淋巴瘤 (DLBCL)。为了增加持久的抗肿瘤反应，我们之前设计了串联 CART19/20 细胞并显示出更长的无进展生存期。然而，一部分接受 CART19/20 治疗的患者最终会进展并需要挽救治疗。在本研究中，我们分析了 5 名复发/难治性 DLBCL 患者的数据，这些患者在 CART19/20 治疗后出现疾病进展或复发，然后用 PD-1 阻断抗体作为补救治疗。五名患者中有两名在抗 PD-1 治疗后获得完全缓解，其中一名患者持续缓解超过 21 个月。一名患者获得了部分缓解，另外两名患者疾病进展。未观察到≥ 3 级治疗相关不良事件或细胞因子释放综合征。肿瘤标本的免疫组织化学显示，与无反应者相比，抗 PD-1 治疗有反应的患者的 PD-1/PD-L1 表达更高。抗 PD-1 治疗后，反应者的循环 T 细胞被激活，未检测到 CART19/20 细胞的显着扩增。我们的数据表明，PD-1 阻断疗法对 CAR T 细胞治疗失败后的复发/难治性 DLBCL 患者有效，这些患者在肿瘤细胞中具有 PD-L1 表达并且在肿瘤浸润的 T 细胞中具有高 PD-1 水平。抗 PD-1 治疗后，反应者的循环 T 细胞被激活，未检测到 CART19/20 细胞的显着扩增。我们的数据表明，PD-1 阻断疗法对 CAR T 细胞治疗失败后的复发/难治性 DLBCL 患者有效，这些患者在肿瘤细胞中具有 PD-L1 表达并且在肿瘤浸润的 T 细胞中具有高 PD-1 水平。抗 PD-1 治疗后，反应者的循环 T 细胞被激活，未检测到 CART19/20 细胞的显着扩增。我们的数据表明，PD-1 阻断疗法对 CAR T 细胞治疗失败后的复发/难治性 DLBCL 患者有效，这些患者在肿瘤细胞中具有 PD-L1 表达并且在肿瘤浸润的 T 细胞中具有高 PD-1 水平。