Department of Haematology, University College London Hospital, London, United Kingdom.
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Semin Hematol. 2023 Nov;60(5):313-321. doi: 10.1053/j.seminhematol.2023.11.003. Epub 2023 Dec 1.
Central nervous system (CNS) lymphoma has traditionally had very poor outcomes however advances in management have resulted in dramatic improvements and long-term survival of patients. We describe the evidence for treatment strategies for these aggressive disorders. In primary CNS lymphoma there are randomized trial data to inform treatment decisions but these are lacking to guide management in secondary CNS lymphoma. Dynamic assessment of patient fitness and frailty is key throughout treatment, alongside delivery of CNS-bioavailable therapy and enrolment in clinical trials, at each stage of the disease. Intensive high-dose methotrexate-containing induction followed by consolidation with autologous stem cell transplantation with thiotepa-based conditioning is recommended for patients who are fit. Less intensive chemoimmunotherapy, novel agents (including Bruton tyrosine kinase inhibitors, cereblon targeting immunomodulatory agents, and checkpoint inhibitors in the context of clinical trials), and whole brain radiotherapy may be reserved for less fit patients or disease which is chemoresistant. Data regarding the efficacy of chimeric antigen receptor T-cells therapy is emerging, and concerns regarding greater toxicity have not been realized. Future areas of prospective studies include the identification of those at high risk of developing CNS lymphoma, management in elderly or frail patients as well as incorporating novel agents into regimens, particularly for those with chemoresistant disease.
中枢神经系统（CNS）淋巴瘤的传统预后非常差，但治疗方法的进步已经显著改善了患者的长期生存。我们描述了这些侵袭性疾病的治疗策略的证据。在原发性 CNS 淋巴瘤中，有随机临床试验数据来为治疗决策提供信息，但在继发性 CNS 淋巴瘤中，缺乏这些数据来指导管理。在整个治疗过程中，对患者的健康状况和虚弱程度进行动态评估是关键，同时还要提供可到达中枢神经系统的治疗药物，并在疾病的每个阶段都要参加临床试验。对于身体状况良好的患者，建议采用高强度含甲氨蝶呤的诱导治疗，随后进行自体干细胞移植巩固治疗，采用噻替派为基础的预处理方案。对于身体状况较差或对化疗耐药的患者，可以选择较不强烈的化疗免疫治疗、新型药物（包括布鲁顿酪氨酸激酶抑制剂、靶向 cereblon 的免疫调节药物，以及临床试验中的检查点抑制剂）和全脑放疗。嵌合抗原受体 T 细胞治疗的疗效数据正在出现，而且尚未发现更大毒性的相关担忧。未来前瞻性研究的领域包括确定那些发生 CNS 淋巴瘤风险较高的患者，以及在老年或体弱患者中的管理，以及将新型药物纳入治疗方案，特别是对于那些对化疗耐药的患者。
