原发性中枢神经系统淋巴瘤药物治疗的研究进展

doi:10.19803/j.1672-8629.20260016

摘要/Abstract

摘要： 目的探讨原发性中枢神经系统淋巴瘤（Primary Central Nervous System Lymphoma, PCNSL）的药物治疗现状及治疗策略研究进展,为临床安全合理用药提供参考。方法围绕PCNSL治疗药物的作用机制、临床疗效、安全性进行系统分析,以克服血脑屏障（BBB）和肿瘤异质性两大核心挑战为贯穿主线,结合文献研究阐述其临床应用现状等。结果在PCNSL治疗中,以高剂量甲氨蝶呤为核心的化疗方案是基础治疗手段,该药物可穿透BBB改善患者预后;但单一用药存在疗效局限及不良反应,因此联合其他化疗药物、放疗或靶向治疗已成为主要发展方向,该治疗模式可增强肿瘤杀伤效应并延长患者无进展生存期。靶向治疗（BTK抑制剂）及免疫治疗为PCNSL治疗开辟新路径,尤其适用于复发或难治性病例,可丰富治疗选择,改善传统化疗耐药问题。嵌合抗原受体T细胞（Chimeric Antigen Receptor T-Cell, CAR-T）疗法作为突破性精准免疫治疗技术,通过修饰自体免疫细胞实现对肿瘤细胞的精准杀伤,在部分难治性PCNSL中展现出显著疗效。结论 PCNSL的药物治疗正处于快速发展期,传统化疗与新兴靶向治疗、免疫治疗相结合的多模态治疗策略,为改善PCNSL患者预后提供参考。

关键词: 原发性中枢神经系统淋巴瘤, 甲氨蝶呤, 化疗, 药物治疗, 嵌合抗原受体T细胞疗法, 靶向治疗, 免疫治疗

Abstract: Objective To summarize the current drug therapies for and research progress in treatment strategies for primary central nervous system lymphoma (PCNSL) so as to provide a reference for the safe and rational clinical use of drugs. Methods The mechanism of action, clinical efficacy, and safety of PCNSL therapeutic drugs were analyzed. By focusing on the challenges posed by the blood-brain barrier (BBB) and tumor heterogeneity, this study elaborated the current clinical applications based on the latest literature. Results Chemotherapy regimens that revolved around on high-dose methotrexate (HD-MTX) were the basic approaches to PCNSL. This drug could improve the prognosis of patients by crossing the blood-brain barrier. However, single-drug use had both limitations in efficacy and toxic side effects. Therefore, combined therapy (such as combination with other chemotherapeutic drugs, radiotherapy or targeted therapy) became the mainstream one, which could enhance the tumor-killing effect and prolong the progression-free survival (PFS) of patients. Targeted therapy (e.g., Bruton’s tyrosine kinase inhibitor, BTKi) and immunotherapy opened up new avenues for PCNSL treatment, which were particularly effective for relapsed or refractory PCNSL cases. They could not only increase clinical treatment options, but also mitigate the resistance to traditional chemotherapy. As a breakthrough precision immunotherapy technology, chimeric antigen receptor T-cell (CAR-T) therapy was capable of precise killing of tumor cells by modifying the patient’s autologous immune cells, and showed significant efficacy in some patients with refractory PCNSL. Conclusion Drug therapy for PCNSL is under rapid development. The multimodal treatment strategy combining traditional chemotherapy with emerging targeted therapy and immunotherapy provides a new line of thought for improving the prognosis of PCNSL patients.

Key words: Primary Central Nervous System Lymphoma (PCNSL), Methotrexate (MTX), Chemotherapy, Drug Therapy, Chimeric Antigen Receptor T-Cell (CAR-T) Therapy, Targeted Therapy, Immunotherapy

中图分类号:

高磊, 张敏, 任晓辉, 刘潜. 原发性中枢神经系统淋巴瘤药物治疗的研究进展[J]. 中国药物警戒, 2026, 23(10): 1081-1085.

Gao Lei, Zhang Min, Ren Xiaohui, Liu Qian. Research progress in drug therapy for primary central nervous system lymphoma[J]. Chinese Journal of Pharmacovigilance, 2026, 23(10): 1081-1085.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://zgywjj.magtechjournal.com/CN/10.19803/j.1672-8629.20260016

https://zgywjj.magtechjournal.com/CN/Y2026/V23/I10/1081

参考文献

[1] Shah T, Venur V A.Central nervous system lymphoma[J]. Semin Neurol, 2023, 43(6): 825-832.
[2] Bai Jiefei, Feng Ru, Wang Ting, et al.Treatment of refractory diffuse large B-cell lymphoma involving the central nervous system with polatuzumab vedotin-based regimen: a case report and literature review[J]. Chinese Journal of Hematology(中华血液学杂志), 2024, 45(9): 864-866.
[3] Mohammed Saleh M, Rasheed W, Alhayli S, et al.Programmed death inhibitors in CNS B-cell lymphoma: a literature review[J]. Blood Rev, 2025, 74: 101321.
[4] Wang M Y, Qu Y, Hu D R, et al.Nanomedicine applications in treatment of primary central nervous system lymphoma: current state of the art[J]. J Biomed Nanotechnol, 2021, 17(8): 1459-1485.
[5] Xia Yong, Li Xue, Jiang Ning, et al.A novel bruton’s tyrosine kinase inhibitor JDB175 shows potent efficacy to suppress central nervous system lymphoma[J]. MedComm, 2023, 4(6): e424.
[6] Faria M J, Rita D, Rui B, et al.Optimum methotrexate exposure in patients with suspected or confirmed CNS invasive hematological malignancies: a systematic critical review[J]. Ther Drug Monit, 2023, 45(3): 287-292.
[7] Yang H, Xun Y, Yang A P, et al.Advances and challenges in the treatment of primary central nervous system lymphoma[J]. J Cell Physiol, 2020, 235(12): 9143-9165.
[8] Liu N P, Jiang C, Yao X F, et al.Single-cell landscape of primary central nervous system diffuse large B-cell lymphoma[J]. Cell Discov, 2023, 9(1): 55.
[9] Liang F, Zhang X T, Ping A N, et al.Plasmablast-like lymphoma cells as a distinct subpopulation confers multidrug resistance in PCNSL[J]. Neuro Oncol, 2025, 27(11): 2927-2942.
[10] Schaff L R, Grommes C.Update on novel therapeutics for primary CNS lymphoma[J]. Cancers (Basel), 2021, 13(21): 5372.
[11] Wirsching H G, Weller M, Balabanov S, et al.Targeted therapies and immune checkpoint inhibitors in primary CNS lymphoma[J]. Cancers (Basel), 2021, 13(12): 3073.
[12] Ljubimov V A, Sun T, Wang J, et al.Blood-brain barrier crossing biopolymer targeting c-Myc and anti-PD-1 activate primary brain lymphoma immunity: artificial intelligence analysis[J]. J Control Release, 2025, 381: 113611.
[13] Grommes C.Central nervous system lymphomas[J]. Continuum (Minneap Minn), 2020, 26(6): 1476-1494.
[14] Li Q, Ma J J, Ma Y, et al.Improvement of outcomes of an escalated high-dose methotrexate-based regimen for patients with newly diagnosed primary central nervous system lymphoma: a real-world cohort study[J]. Cancer Manag Res, 2021, 13: 6115-6122.
[15] Spalato M, Italiano A.The safety of current pharmacotherapeutic strategies for osteosarcoma[J]. Expert Opin Drug Saf, 2021, 20(4): 427-438.
[16] Kondo E.Primary central nervous system lymphoma: advances in treatment strategies[J]. Rinsho Ketsueki, 2020, 61(5): 510-519.
[17] Takahashi M, Sumitani R, Hori T, et al.Intravenous busulfan-based conditioning with autologous stem cell transplantation for refractory B-cell lymphoma with central nervous system involvement[J]. J Med Invest, 2021, 68(1.2): 196-201.
[18] Sasaki N, Kobayashi K, Saito K, et al.Consecutive single-institution case series of primary central nervous system lymphoma treated by R-MPV or high-dose methotrexate monotherapy[J]. Jpn J Clin Oncol, 2020, 50(9): 999-1008.
[19] Yuan X G, Yu T, Huang Y R, et al.Rituximab with high-dose methotrexate is effective and cost-effective in newly diagnosed primary central nervous system lymphoma[J]. Sci Rep, 2022, 12(1): 21541.
[20] Kim P, Omuro A.Consolidation therapy in primary central nervous system lymphoma[J]. Curr Treat Options Oncol, 2020, 21(9): 74.
[21] Hu Beini, Yang Xiang, Yuan Yongping, et al.New advances in the treatment of primary central nervous system lymphoma-review[J]. Journal of Experimental Hematology(中国实验血液学杂志), 2021, 29(2): 633-637.
[22] Elgohary G, Yang Y, Gergis M, et al.Chimeric antigen receptor T-cell therapy for large B-cell lymphoma patients with central nervous system involvement, a systematic review and meta-analysis[J]. Clin Lymphoma Myeloma Leuk, 2024, 24(4): e142-e151.
[23] Takigawa K, Kawano N, Mori Y, et al.A case of successful CAR-T cell therapy for early isolated CNS recurrence of DLBCL with persistent CAR-T cells[J]. Blood Cell Ther, 2024, 7(2): 37-40.
[24] Zheng M Z, Yang Z Q, Cai S L, et al.Blood-brain barrier and blood-brain tumor barrier penetrating peptide-drug conjugate as targeted therapy for the treatment of lung cancer brain metastasis[J]. Lung Cancer, 2024, 196: 107957.
[25] Hernández-Verdin I, Morales-Martínez A, Hoang-Xuan K, et al.Primary central nervous system lymphoma: advances in its pathogenesis, molecular markers and targeted therapies[J]. Curr Opin Neurol, 2022, 35(6): 779-786.
[26] Sasaki N, Nagane M.Perspectives on precision medicine in primary central nervous system lymphoma[J]. No Shinkei Geka, 2022, 50(1): 51-60.
[27] Roschewski M, Hodson D J.Diffuse large B-cell lymphoma involving the central nervous system: biologic rationale for targeted therapy[J]. Haematologica, 2024, 109(2): 388-400.
[28] Jaradat J H, Alkhawaldeh I M, Al-Bojoq Y, et al.Efficacy and safety of ibrutinib in central nervous system lymphoma: a systematic review and meta-analysis[J]. Crit Rev Oncol Hematol, 2024, 206: 104597.
[29] Zhong L, Lu A Q, Lu X Y, et al.Molecular mechanisms and therapeutic prospects of immunotherapy and targeted therapy in primary central nervous system lymphoma[J]. Technol Cancer Res Treat, 2025, 24: 15330338251319394.
[30] Taranto E P, Barta S K, Bhansali R S.Central nervous system relapse in T and NK cell lymphomas[J]. Curr Hematol Malig Rep, 2023, 18(6): 243-251.
[31] Yang C W, Ren X H, Cui Y, et al.New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma[J]. Front Immunol, 2025, 16: 1438001.
[32] Ramadan S, Radice T, Ismail A, et al.Advances in therapeutic strategies for primary CNS B-cell lymphomas[J]. Expert Rev Hematol, 2022, 15(4): 295-304.
[33] Tan T J, Layhadi J A, Shamji M H.Mechanisms and biomarkers of subcutaneous immunotherapy and sublingual immunotherapy in allergen immunotherapy[J]. Allergy Asthma Proc, 2022, 43(4): 254-259.
[34] Mercadal S, Ahn K W, Allbee-Johnson M, et al.Outcomes of patients with primary central nervous system lymphoma following CD19-targeted chimeric antigen receptor T-cell therapy[J]. Haematologica, 2025, 110(1): 218-221.
[35] Lyu L W, Wu Y C, Shi H, et al.Efficacy and safety of chimeric antigen receptor T-cells treatment in central nervous system lymphoma: a PRISMA-compliant single-arm meta-analysis[J]. Cancer Immunol Immunother, 2023, 72(1): 211-221.
[36] Cassanello G, Luttwak E, Brown S, et al.Outcomes of CD19 CAR-T therapy in central nervous system lymphoma: insights from a multicentre experience[J]. Br J Haematol, 2025, 207(2): 525-534.
[37] Zheng J, Xiao Y, Wu X, et al.Double systemic cytokine release syndrome following sequential infusion of anti-CD22 and anti-CD19 chimeric antigen receptor T-cells after autologous hematopoietic stemcell transpl-antation for a central diffuse large B-cell lymphoma patient: a case report and literature review[J]. Front Immunol, 2023, 14: 1098815.
[38] Tan Y, Pan J, Deng B P, et al.Toxicity and effectiveness of CD19 CAR T therapy in children with high-burden central nervous system refractory B-ALL[J]. Cancer Immunol Immunother, 2021, 70(7): 1979-1993.
[39] Zhou J, Wang Z H, Wang Hanyu, et al.Sustained efficacy of chimeric antigen receptor T-cell therapy in central nervous system lymphoma: a systematic review and meta-analysis of individual data[J]. Front Pharmacol, 2023, 14: 1331844.
[40] Shi H, Sun X F, Wu Y C, et al.Targeting the tumor microenvironment in primary central nervous system lymphoma: implications for prognosis[J]. J Clin Neurosci, 2024, 124: 36-46.
[41] Planken S, Faict S, Trullemans F, et al.Prolonged responses in central nervous system relapsed diffuse large B-cell lymphoma after chimeric antigen receptor T-cell therapy using targeted treatments[J]. Cureus, 2024, 16(8): e66291.