BTK inhibitor combined with anti‑PD‑1 monoclonal antibody for the treatment of CD20‑negative primary central nervous system lymphoma: A case report

Feng,Lan; Gao,Xiaohui; Jiao,Zhiyun; Wang,Zheng; Min,Fenglin

doi:10.3892/ol.2022.13634

BTK inhibitor combined with anti‑PD‑1 monoclonal antibody for the treatment of CD20‑negative primary central nervous system lymphoma: A case report

Authors:
- Lan Feng
- Xiaohui Gao
- Zhiyun Jiao
- Zheng Wang
- Fenglin Min
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Affiliations: Department of Hematology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China, Department of Radiology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China, Department of Pathology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu 225009, P.R. China, Department of Hematology, Yangzhou Hospital of Traditional Chinese Medicine, Yangzhou, Jiangsu 225012, P.R. China
Published online on: December 15, 2022 https://doi.org/10.3892/ol.2022.13634
Article Number: 48
Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

CD20‑negative diffuse large B‑cell lymphoma (DLBCL) is a rare type of lymphoproliferative disorder characterized by a high degree of aggressiveness, a tendency for extranodal invasion and chemotherapeutic resistance. CD20‑negative DLBCL originating from the nervous system is rarer. In primary central nervous system lymphoma (PCNSL), >90% of cases are histologically classified as DLBCL. The present study reports the case of a 65‑year‑old female with CD20‑negative PCNSL, whose primary clinical symptom was a persistent headache. Serum tests for human immunodeficiency virus, Epstein‑Barr virus‑DNA, human herpesvirus 8, hepatitis B and hepatitis C were negative. Cranial magnetic resonance imaging suggested multiple intracranial occupancies. The neoplastic cells were found to be positive for CD19, CD79α, Bcl‑2 (~92%) and c‑Myc (~50%), while showing negative results for CD20, CD138, programmed cell death protein 1 (PD‑1) and programmed cell death receptor 1 ligand 1 (PD‑L1). The Ki‑67 proliferation index was >80%. In the tumor microenvironment, <10% of the tumor‑associated macrophages expressed PD‑L1. The number of PD‑1‑positive tumor‑infiltrating lymphocytes was 30‑40 cells according to high‑power field microscopy. The patient's disease progressed during methotrexate‑based treatment, leading to a change in the treatment regimen to the Bruton tyrosine kinase inhibitor, zanubrutinib, combined with the anti‑PD‑1 monoclonal antibody tislelizumab. After two courses of the combined treatment, the patient achieved complete remission (CR) and continued to receive consolidation treatment. In the 20 months of follow‑up since CR was achieved, the patient's general condition was good and the disease was in continuous remission. The present case report and literature review show that a combination of drugs targeting different mechanisms may be used to treat PCNSL to prolong patient survival time. The mechanism of the enhanced efficacy of a combination of the two drugs may be related to the enhancement of antitumor T‑cell immune responses and reversal of T‑cell immune metabolic dysfunctions by the inhibition of glycolysis.

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