Shi Hui, Zheng Peihao, Fu Zhonghua, Cao Miaomiao, Yang Fan, Guo Yuelu, Liu Rui, Ma Lixia, Feng Shaomei, Tao Xiuyan, Deng Biping, Lei Yang, Dou Yimeng, Zhang Xuenan, Ke Xiaoyan, Hu Kai
Department of Lymphoma and Myeloma Research Center, Beijing GoBroad Hospital, No. 4 Building, Kexueyuan Street, Changping District, Beijing City, 102200, China.
Department of Lymphoma and Myeloma Research Center, Beijing Gobroad Boren Hospital, Beijing, 100070, China.
Ann Hematol. 2025 Apr;104(4):2495-2505. doi: 10.1007/s00277-025-06378-y. Epub 2025 Apr 25.
Relapsed or refractory central nervous system B-cell lymphoma (r/r CNS-BL), including primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL), remains a significant therapeutic challenge with limited treatment options and poor prognosis. This study investigated the combination of whole-brain radiotherapy (WBRT) and chimeric antigen receptor T-cell (CAR-T) therapy in 27 r/r CNS-BL patients. Peripheral blood mononuclear cells were collected before radiotherapy to prepare CAR-T cells. Patients then received whole-brain radiotherapy (WBRT), with or without local boost, followed by CAR-T cell infusion at least one week after radiotherapy completion. Post-CAR-T therapy, the optimal objective response rate (ORR) increased to 88.9%, and the optimal CR rate reached 85.2%. With a median follow-up of 12 months, the median progression-free survival (PFS) and overall survival (OS) were not reached (NR), and the 1-year estimated PFS and OS rate were 61.3% and 56.6%, respectively. Cytokine release syndrome (CRS) occurred in 48.1% of patients. Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 29.6% of patients, with only 3.7% on grade 4, all of whom recovered after treatment. This study demonstrates that the combination of WBRT and CAR-T therapy offers a promising therapeutic strategy for r/r CNS-BL patients, improving remission rates and providing a well-tolerated treatment option.
复发或难治性中枢神经系统B细胞淋巴瘤（r/r CNS-BL），包括原发性中枢神经系统淋巴瘤（PCNSL）和继发性中枢神经系统淋巴瘤（SCNSL），仍然是一个重大的治疗挑战，治疗选择有限且预后较差。本研究调查了27例r/r CNS-BL患者接受全脑放疗（WBRT）与嵌合抗原受体T细胞（CAR-T）疗法联合治疗的情况。放疗前采集外周血单个核细胞以制备CAR-T细胞。然后患者接受全脑放疗（WBRT），有或无局部加强照射，放疗完成后至少1周进行CAR-T细胞输注。CAR-T治疗后，最佳客观缓解率（ORR）提高到88.9%，最佳完全缓解率（CR）达到85.2%。中位随访12个月时，无进展生存期（PFS）和总生存期（OS）均未达到（NR），1年估计PFS率和OS率分别为61.3%和56.6%。48.1%的患者发生了细胞因子释放综合征（CRS）。29.6%的患者观察到免疫效应细胞相关神经毒性综合征（ICANS），4级仅3.7%，所有患者治疗后均康复。本研究表明，WBRT与CAR-T疗法联合为r/r CNS-BL患者提供了一种有前景的治疗策略，提高了缓解率并提供了耐受性良好的治疗选择。
