Prognostic impact of PD-L1 expression in primary gastric and intestinal diffuse large B-cell lymphoma
Prognostic impact of PD-L1 expression in primary gastric and intestinal diffuse large B-cell lymphoma
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DOI：
10.1007/s00535-019-01616-3
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发表时间：
2020-01-01
影响因子：
6.3
通讯作者：
Fujishiro, Mitsuhiro
中科院分区：
文献类型：
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作者：
Ishikawa, Eri;Nakamura, Masanao;Fujishiro, Mitsuhiro
背景弥漫性大B细胞淋巴瘤（DLBCL）是一种异质性疾病，是最常见的胃肠道淋巴瘤。胃和肠DLBCL（giDLBCL）患者的预后/预测指标存在争议，超出其解剖部位。我们比较了gDLBCL病例，并调查了新出现的指标的临床效用，重点是程序性细胞死亡配体1（PD-L1）表达。方法本回顾性研究包括1995年至2018年接受含利妥昔单抗化疗的174例原发性胃（n = 129）或肠（n = 45）DLBCL患者。肠DLBCL（iDLBCL）患者中晚期Lugano分期的发生率显著较高，（71% vs 37%，P < 0.001），穿孔（13% vs. 0.8%，P = 0.001），微环境免疫细胞上的PD-L1表达（miPD-L1，70% vs 46%，P = 0.008）、CD 10阳性（47% vs 28%，P = 0.027）和CD 5阳性（9% vs 1.6%，P = 0.040）。iDLBCL患者的无进展生存期（PFS）和总生存期（OS）显著低于gDLBCL患者（分别为P = 0.0338和P = 0.0077）。在174例早期复发和/或侵袭性临床病程的病例中，仅3例（2%）检测到肿瘤细胞上的PD-L1表达;然而，miPD-L1阳性病例的OS显著优于miPD-L1阴性gDLBCL和iDLBCL病例（分别为P = 0.0281和P = 0.0061）。多因素分析显示，miPD-L1阴性（P = 0.030）是影响giDLBCL患者OS的独立不良预后因素。结论在接受含利妥昔单抗化疗的giDLBCL患者中，疾病的解剖部位不影响预后;而miPD-L1表达对预后有有利影响。
Background Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease and the most common gastrointestinal lymphoma. The prognostic/predictive indicators among patients with gastric and intestinal DLBCL (giDLBCL) are controversial beyond their anatomical sites. We compared giDLBCL cases and investigated the clinical utility of newly emerging indicators with an emphasis on programmed cell death ligand 1 (PD-L1) expression.Methods This retrospective study included 174 patients with primary gastric (n = 129) or intestinal (n = 45) DLBCL treated with rituximab-containing chemotherapy between 1995 and 2018.Results Compared with gastric DLBCL (gDLBCL) cases, patients with intestinal DLBCL (iDLBCL) had a significantly higher rate of advanced Lugano stage (71% vs 37%, P < 0.001), perforation (13% vs. 0.8%, P = 0.001), PD-L1 expression on microenvironment immune cells (miPD-L1, 70% vs 46%, P = 0.008), CD10 positivity (47% vs 28%, P = 0.027), and CD5 positivity (9% vs 1.6%, P = 0.040). The iDLBCL patients showed significantly worse progression-free survival (PFS) and overall survival (OS) than gDLBCL cases (P = 0.0338 and P = 0.0077, respectively). PD-L1 expression on tumor cells was detected in only 3 (2%) of 174 cases with early relapse and/or an aggressive clinical course; whereas, miPD-L1-positive cases had significantly better OS than the miPD-L1-negative gDLBCL and iDLBCL cases (P = 0.0281 and P = 0.0061, respectively). Multivariate analysis revealed that miPD-L1 negativity (P = 0.030) was an independent adverse prognostic factor for OS in giDLBCL.Conclusions The anatomical site of disease did not influence outcome in giDLBCL cases treated with rituximab-containing chemotherapy; while, miPD-L1 expression had a favorable impact on the outcome.