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比较 EBV 阳性和阴性复发或难治性非霍奇金淋巴瘤患者使用帕博利珠单抗的疗效。

Comparison of Efficacy of Pembrolizumab between Epstein-Barr Virus‒Positive and ‒Negative Relapsed or Refractory Non-Hodgkin Lymphomas.

机构信息

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Cancer Res Treat. 2019 Apr;51(2):611-622. doi: 10.4143/crt.2018.191. Epub 2018 Jul 20.

Abstract

PURPOSE

Pembrolizumab, a programmed cell death protein 1 (PD1) inhibitor inhibits the interplay between PD1 of T-cell and programmed cell death ligand 1 (PDL1) on tumor cells. Although pembrolizumab has been tried to various subtypes of non-Hodgkin lymphoma (NHL), realworld data about the efficacy of pembrolizumab in NHL patients are limited.

MATERIALS AND METHODS

We analyzed the outcome of 30 relapsed or refractory NHL patients treated with pembrolizumab, and compared the outcome between Epstein-Barr virus (EBV)‒positive and negative subtypes because EBV infection of tumor cells can upregulate PDL1 expression.

RESULTS

Seven patients with EBV-positive NHL showed a response including NK/T-cell lymphoma (6/14, 44%) and primary mediastinal B-cell lymphoma (1/4, 25%) whereas EBV-negative subtypes did not respond such as diffuse large B-cell lymphoma and T-lymphoblastic lymphoma. We also evaluated PDL1 expression using tumor tissue of 76 patients. High PDL1 expression (positive staining of > 50% of tumor cells) was more frequent in NK/T-cell lymphoma and primary mediastinal B-cell lymphoma than other subtypes. Thus, PDL1 expression was significantly higher in EBV-positive (18/32, 56%) than EBV-negative NHL (4/38, 11%, p < 0.001). Furthermore, NK/T-cell lymphoma patients with high PDL1 expression showed a higher response (4/6, 67%) than those with low PDL1 expression (1/5, 20%).

CONCLUSION

Pembrolizumab could be useful as a salvage treatment for relapsed or refractory EBV-positive NHL, especially NK/T-cell lymphoma. However, its efficacy in EBV-negative NHL with low or absent PDL1 expression is still not clear although pembrolizumab could be a potential treatment option for relapsed or refractory NHL.

摘要

目的

帕博利珠单抗是一种程序性死亡蛋白 1(PD1)抑制剂,可抑制 T 细胞上的 PD1 与肿瘤细胞上的程序性死亡配体 1(PDL1)之间的相互作用。尽管帕博利珠单抗已尝试用于各种非霍奇金淋巴瘤(NHL)亚型,但关于帕博利珠单抗在 NHL 患者中的疗效的真实世界数据有限。

材料和方法

我们分析了 30 例接受帕博利珠单抗治疗的复发或难治性 NHL 患者的结果,并比较了 EBV 阳性和阴性亚型之间的结果,因为肿瘤细胞中的 EBV 感染可上调 PDL1 表达。

结果

7 例 EBV 阳性 NHL 患者出现了包括 NK/T 细胞淋巴瘤(6/14,44%)和原发性纵隔 B 细胞淋巴瘤(1/4,25%)在内的缓解,而 EBV 阴性亚型则没有缓解,如弥漫性大 B 细胞淋巴瘤和 T 淋巴母细胞淋巴瘤。我们还评估了 76 例患者的肿瘤组织中的 PDL1 表达。NK/T 细胞淋巴瘤和原发性纵隔 B 细胞淋巴瘤的高 PDL1 表达(肿瘤细胞阳性染色>50%)比其他亚型更常见。因此,EBV 阳性 NHL(18/32,56%)中的 PDL1 表达明显高于 EBV 阴性 NHL(4/38,11%,p<0.001)。此外,高 PDL1 表达的 NK/T 细胞淋巴瘤患者的缓解率更高(4/6,67%),而低 PDL1 表达的患者的缓解率更低(1/5,20%)。

结论

帕博利珠单抗可作为复发或难治性 EBV 阳性 NHL,特别是 NK/T 细胞淋巴瘤的挽救治疗方法。然而,对于 EBV 阴性 NHL 患者,其疗效在低表达或无表达 PDL1 的患者中仍不清楚,尽管帕博利珠单抗可能是复发或难治性 NHL 的潜在治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/261a/6473267/dfb90d91a5a2/crt-2018-191f1.jpg

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