Prognostic impact of PD-L1 expression in primary gastric and intestinal diffuse large B-cell lymphoma

• Published in: Journal of gastroenterology Vol. 55; no. 1; pp. 39 - 50
• Main Authors: Ishikawa, Eri, Nakamura, Masanao, Shimada, Kazuyuki, Tanaka, Tsutomu, Satou, Akira, Kohno, Kei, Sakakibara, Ayako, Furukawa, Kazuhiro, Yamamura, Takeshi, Miyahara, Ryoji, Nakamura, Shigeo, Kato, Seiichi, Fujishiro, Mitsuhiro
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.01.2020; Springer; Springer Nature B.V
• Subjects: Abdominal Surgery; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; B-cell lymphoma; B7-H1 Antigen - metabolism; Biomarkers, Tumor - metabolism; Cancer; Care and treatment; CD5 antigen; Cell death; Chemotherapy; Colorectal Surgery; Comparative analysis; Female; Follow-Up Studies; Gastroenterology; Hepatology; Humans; Immunohistochemistry; In Situ Hybridization; Intestinal Neoplasms - diagnosis; Intestinal Neoplasms - drug therapy; Intestinal Neoplasms - metabolism; Intestinal Neoplasms - mortality; Intestine; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - mortality; Male; Medical colleges; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Middle Aged; Monoclonal antibodies; Multivariate Analysis; Non-Hodgkin's lymphomas; Original Article—Alimentary Tract; PD-L1 protein; Prognosis; Retrospective Studies; Rituximab; Rituximab - therapeutic use; Stomach Neoplasms - diagnosis; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Stomach Neoplasms - mortality; Surgical Oncology; Survival Analysis; Targeted cancer therapy; Tumor cells; PD-L1; Gastric lymphoma; Gastrointestinal lymphoma; DLBCL; Intestinal lymphoma
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-019-01616-3

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.