A prognostic model, including the EBV status of tumor cells, for primary gastric diffuse large B‐cell lymphoma in the rituximab era

• Published in: Cancer medicine (Malden, MA) Vol. 7; no. 7; pp. 3510 - 3520
• Main Authors: Ishikawa, Eri, Tanaka, Tsutomu, Shimada, Kazuyuki, Kohno, Kei, Satou, Akira, Eladl, Ahmed E., Sakakibara, Ayako, Furukawa, Kazuhiro, Funasaka, Kohei, Miyahara, Ryoji, Nakamura, Masanao, Goto, Hidemi, Nakamura, Shigeo, Kato, Seiichi, Hirooka, Yoshiki
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.07.2018; John Wiley and Sons Inc; Wiley
• Subjects: Apoptosis; B-cell lymphoma; Cancer Prevention; Chemotherapy; Clinical trials; diffuse large B‐cell lymphoma; Epstein‐Barr virus; gastric lymphoma; Gastrointestinal tract; Hybridization; Immunotherapy; Lymphocytes B; Lymphoma; Medical prognosis; Monoclonal antibodies; Original Research; PD-L1 protein; PD‐L1; Risk groups; Rituximab; Targeted cancer therapy; Tumor cells; PD-L1; Epstein-Barr virus; diffuse large B-cell lymphoma; gastric lymphoma; rituximab
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.1595

EBV‐positive diffuse large B‐cell lymphoma (DLBCL), not otherwise specified (NOS), often affects the gastrointestinal tract. However, the prognostic significance of EBV associated with primary gastric DLBCL (gDLBCL) has not been established. This retrospective study included 240 patients with primary gDLBCL, diagnosed between 1995 and 2015. Tumor specimens were analyzed with EBER in situ hybridization. In 25 (10%) cases, tumor cells harbored EBV. The EBV+ group more frequently exhibited programmed death‐ligand 1 (PD‐L1) expression in microenvironment immune cells, but not tumor cells, compared to the EBV− group (86% vs 43%, P = .006). Among 156 patients that received rituximab‐containing chemotherapy, the EBV+ group had a significantly worse overall survival (OS) than the EBV− group (P = .0029). Multivariate analyses identified 3 independent adverse prognostic factors of OS: multiple gastric lesions (P = .002), EBER positivity (P = .003), and B symptoms (P = .018). These factors were combined to develop a gDLBCL prognostic (gDLP) model that significantly stratified the patients into 3 distinct risk groups (Scores: good = 0, intermediate = 1, and poor = 2/3, P < .0001) with 5‐year OS rates of 100%, 81%, and 39%, respectively. Patients with EBV+ gDLBCL commonly exhibited microenvironmental PD‐L1 expression and showed a significantly worse prognosis than subjects with EBV− gDLBCL. Our gDLP model, which included EBV+ tumor cells, provided good predictions of clinical outcome and may be useful for selecting patients in trials in the immune‐oncology era. EBV+ gastric DLBCL was significantly associated with PD‐L1 expression in microenvironmental immune cells and with poor survival. Our primary gastric DLBCL prognostic (gDLP)‐model, which included EBV‐harboring tumor cells, multiple gastric lesions, and B symptoms, significantly stratified patients with primary gastric DLBCL into 3 distinct risk groups with different survival rates, in the era of rituximab.