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

Eri Ishikawa,Tsutomu Tanaka,Shigeo Nakamura,Ayako Sakakibara,Kei Kohno,Akira Satou,Seiichi Kato,Kohei Funasaka,Ahmed E Eladl,Masanao Nakamura,Kazuhiro Furukawa,Kazuyuki Shimada,Yoshiki Hirooka,Hidemi Goto,Ryoji Miyahara

doi:10.1002/cam4.1595

Abstract

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.

Highlights

Within the gastrointestinal (GI) tract, the stomach is the most common site of non-H odgkin lymphoma (NHL)
We aimed to develop a gastric DLBCL (gDLBCL)-specific model designed for the rituximab era, which could be useful in selecting patients for clinical trials for immune-oncology therapeutics
We found no significant difference in clinicopathological findings between the Epstein- Barr virus (EBV)+ and EBV− gDLBCL subgroups, except for the endoscopic features and microenvironmental progressive disease (PD)-L1 expression (Table 1)

Summary

| INTRODUCTION

Within the gastrointestinal (GI) tract, the stomach is the most common site of non-H odgkin lymphoma (NHL). The clinicopathological and prognostic significance of EBV associated with primary gastric DLBCL (gDLBCL) has not been well established. In patients with gDLBCL, outcome is typically predicted with the Lugano staging system for GI tract lymphoma and the International Prognostic Index (IPI) for aggressive NHL.[20,21]. These classification systems were devised in the pre-rituximab era; that is, before rituximab was routinely added to chemotherapy, due to its positive impact in patients with DLBCL.[22]. We aimed to develop a gDLBCL-specific model designed for the rituximab era, which could be useful in selecting patients for clinical trials for immune-oncology therapeutics

| MATERIALS AND METHODS

| RESULTS

Findings

| DISCUSSION