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

  • Original Article—Alimentary Tract
  • Published:
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Abstract

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.

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Abbreviations

CR:

Complete remission

DD:

Died of disease

DLBCL:

Diffuse large B-cell lymphoma

DOC:

Died of other causes

EBER:

Epstein-Barr virus-encoded small RNA

EBV:

Epstein-Barr virus

gDLBCL:

Gastric diffuse large B-cell lymphoma

giDLBCL:

Gastric and intestinal diffuse large B-cell lymphoma

iDLBCL:

Intestinal diffuse large B-cell lymphoma

LDH:

Lactate dehydrogenase

miPD-L1:

Programmed cell death ligand 1 expression on microenvironment immune cells

NED:

No evidence of disease

non-ROD24:

Recurrence of disease at 24 months or later

nPD-L1:

Programmed cell death ligand 1 expression on neoplastic cells

OS:

Overall survival

PD-L1:

Programmed cell death ligand 1

PFS:

Progression-free survival

R-containing chemotherapy:

Rituximab-containing chemotherapy

ROD24:

Recurrence of disease within 24 months

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Acknowledgements

The authors thank Y. Katayama, Y. Inagaki, K. Matsubara, and K. Kito for technical assistance and the following collaborators for providing patient clinical data and specimens: Aichi Cancer Center Hospital, Anjo Kosei Hospital, Ekisaikai Hospital, Fujita Health University, Ishikawa Prefectural Central Hospital, Japanese Red Cross Nagoya Daini Hospital, Kani Tono Hospital, Kariya Toyota General Hospital, Koseiren Takaoka Hospital, Matsue City Hospital, Ogaki Municipal Hospital, Okazaki Municipal Hospital, Omihachiman Community Medical Center, Shizuoka Saiseikai General Hospital, Suzuka Chuo General Hospital, Takatsuki General Hospital, Toyota Kosei Hospital, Toyota Memorial Hospital, Toyama Prefectural Central Hospital, Toyohashi Medical center, and Toyohashi Municipal Hospital.

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Author information

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Aichi, Japan

    Eri Ishikawa, Masanao Nakamura, Kazuhiro Furukawa, Ryoji Miyahara & Mitsuhiro Fujishiro

  2. Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan

    Eri Ishikawa, Kei Kohno, Ayako Sakakibara & Shigeo Nakamura

  3. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Kazuyuki Shimada

  4. Department of Endoscopy, Aichi Cancer Center Hospital, Nagoya, Japan

    Tsutomu Tanaka

  5. Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Japan

    Akira Satou

  6. Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan

    Takeshi Yamamura

  7. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan

    Seiichi Kato

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  1. Eri Ishikawa
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  2. Masanao Nakamura
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Contributions

EI, SN, and MF: study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, revision of the manuscript, statistical analysis. SK, KS, AS, and KK: acquisition of data, analysis and interpretation of data. Rest of authors: acquisition of data. All authors approved the final version of the manuscript.

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Correspondence to Eri Ishikawa.

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Ishikawa, E., Nakamura, M., Shimada, K. et al. Prognostic impact of PD-L1 expression in primary gastric and intestinal diffuse large B-cell lymphoma. J Gastroenterol 55, 39–50 (2020). https://doi.org/10.1007/s00535-019-01616-3

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  • DOI: https://doi.org/10.1007/s00535-019-01616-3

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