Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, Hubei, China.
Cancer Immunol Immunother. 2024 Nov 11;74(1):17. doi: 10.1007/s00262-024-03855-7.
Several reports have indicated that chimeric antigen receptor (CAR) T-cell therapy following autologous hematopoietic stem cell transplantation (ASCT) is a promising strategy for refractory/relapsed (r/r) central nervous system lymphoma (CNSL), but the number of reported cases is limited.
The cohort in this retrospective study consisted of 38 patients with r/r CNSL who received CAR T-cell therapy following ASCT at our center between January 2019 and April 2024. Group comparisons of continuous variables were tested using the unpaired Student's t-test or the Mann-Whitney U-test, while categorical variables were analyzed using Fisher's exact test. The Kaplan-Meier method was employed to estimate survival curves, and group comparisons were performed using the log-rank test.
The cohort comprised 38 patients with r/r CNSL, all of whom had active CNS involvement. After therapy, the best overall response rate (ORR) of all patients was 78.9%. Subgroup analysis found that a lower ORR was observed in patients with lactate dehydrogenase levels above the upper limit of normal (60.0% vs. 91.3%, P = 0.039). With a median follow-up of 37.5 months, the estimated 1-year overall survival (OS) and progression-free survival (PFS) rates were 72.8% and 57.4%, respectively. The risk factors associated with PFS was no response to current therapy (adjusted hazard ratio: 22.87, P < 0.001). The incidence rates of severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were both 13.2%. Among the 25 patients with secondary CNSL (SCNSL), the best ORRs were 91.7% for those with CNS lesions only and 61.5% for those with CNS and systemic lesions (P = 0.160), while the estimated 1-year PFS rates were 83.3% and 38.5%, respectively (P = 0.030).
CAR T-cell therapy following ASCT shows promising efficacy for r/r CNSL patients. Besides, SCNSL patients with CNS and systemic lesions have inferior treatment efficacy compared to those with CNS lesions only.
多项研究表明，嵌合抗原受体（CAR）T 细胞疗法在自体造血干细胞移植（ASCT）后用于治疗复发/难治性（r/r）中枢神经系统淋巴瘤（CNSL）是一种很有前景的策略，但报告的病例数量有限。
本回顾性研究的队列包括 2019 年 1 月至 2024 年 4 月期间在我院接受 ASCT 后接受 CAR T 细胞治疗的 38 例 r/r CNSL 患者。连续变量的组间比较采用未配对学生 t 检验或曼-惠特尼 U 检验，分类变量采用 Fisher 确切检验进行分析。采用 Kaplan-Meier 法估计生存曲线，采用对数秩检验进行组间比较。
该队列包括 38 例 r/r CNSL 患者，所有患者均有活动性中枢神经系统受累。治疗后，所有患者的最佳总缓解率（ORR）为 78.9%。亚组分析发现，乳酸脱氢酶水平高于正常值上限的患者 ORR 较低（60.0%比 91.3%，P=0.039）。中位随访 37.5 个月后，估计 1 年总生存率（OS）和无进展生存率（PFS）分别为 72.8%和 57.4%。与 PFS 相关的危险因素是对当前治疗无反应（调整后的危险比：22.87，P<0.001）。严重细胞因子释放综合征和免疫效应细胞相关神经毒性综合征的发生率均为 13.2%。在 25 例继发性 CNSL（SCNSL）患者中，仅 CNS 病变患者的最佳 ORR 为 91.7%，而 CNS 和全身病变患者的最佳 ORR 为 61.5%（P=0.160），估计 1 年 PFS 率分别为 83.3%和 38.5%（P=0.030）。
ASCT 后 CAR T 细胞疗法治疗 r/r CNSL 患者显示出良好的疗效。此外，与仅 CNS 病变患者相比，伴有 CNS 和全身病变的 SCNSL 患者治疗效果较差。
