Zhou Xiaoxi, Yu Qiuxia, Dai Zigang, Wang Jue, Li Chunrui, Huang Liang, Zhang Yicheng, Cao Yang
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Immunotherapy Research Center for Hematologic Diseases of Hubei Province, Wuhan, Hubei, China.
Exp Hematol Oncol. 2024 Oct 13;13(1):100. doi: 10.1186/s40164-024-00538-y.
Relapsed/refractory (R/R) primary and secondary central nervous system lymphomas (PCNSL, SCNSL) are associated with short survival and represent an unmet need, requiring novel effective strategies. We retrospectively compared the safety and efficacy of CD19/22 CAR-T-cell therapy following ASCT (ASCT + CAR-T group), CD19/22 CAR-T-cell cocktail therapy (CAR-T group) and chemoimmunotherapy (CIT group) in treating R/R CNSL patients. Analysis of the differences in clinical characteristics among the three groups revealed that the median age in the CIT group was older than that in the ASCT + CAR-T group and CAR-T group, and the median number of prior lines of therapy in the CIT group was less than that in the other groups. Patients in the two CAR-T-therapy groups exhibited comparable incidences and severities of CRS and ICANS. Grade 4-5 CRS and ICANS were not observed in either CAR-T-cell therapy group. The incidence of Grade 3/4 hematological toxicity in the ASCT + CAR-T and CAR-T groups was greater than that in the CIT group. The ORR was 82.75% in the ASCT + CAR-T group, 60.00% in the CAR-T group and 58.83% in the CIT group. As of December 31, 2022, the median follow-up after therapy was 16.73 months (range, 0.67-42.00 months). The median durations of PFS and OS were not reached in the ASCT + CAR-T group. The median PFS in the CAR-T group was 4.72 months, and OS was not reached. In the CIT group, the median PFS and OS were 6.63 months and 16.77 months, respectively. The 2-year PFS rate of patients in the ASCT + CAR-T group (65.52%) was significantly greater than that of patients in the CAR-T group (30.00%, P = 0.0321) and CIT group (23.53%, P = 0.0043). Our results support the development of CAR-T-cell therapy for R/R CNSL. With the durability of remission and low toxicity, ASCT combined with CAR-T-cell therapy appears to be a more effective and safer treatment option for primary and secondary R/R CNS lymphoma.
复发/难治性（R/R）原发性和继发性中枢神经系统淋巴瘤（PCNSL、SCNSL）患者生存期短，存在未满足的需求，需要新的有效治疗策略。我们回顾性比较了自体造血干细胞移植后CD19/22嵌合抗原受体T细胞（CAR-T）疗法（ASCT + CAR-T组）、CD19/22 CAR-T细胞联合疗法（CAR-T组）和化疗免疫疗法（CIT组）治疗R/R中枢神经系统淋巴瘤患者的安全性和疗效。对三组患者临床特征差异的分析显示，CIT组的中位年龄高于ASCT + CAR-T组和CAR-T组，CIT组既往治疗线数的中位数少于其他组。两个CAR-T治疗组患者的细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）的发生率和严重程度相当。两个CAR-T细胞治疗组均未观察到4-5级CRS和ICANS。ASCT + CAR-T组和CAR-T组3/4级血液学毒性的发生率高于CIT组。ASCT + CAR-T组的客观缓解率（ORR）为82.75%，CAR-T组为60.00%，CIT组为58.83%。截至2022年12月31日,治疗后的中位随访时间为16.73个月（范围0.67-42.00个月）。ASCT + CAR-T组的无进展生存期（PFS）和总生存期（OS）的中位数未达到。CAR-T组的中位PFS为4.72个月，OS未达到。CIT组的中位PFS和OS分别为6.63个月和16.77个月。ASCT + CAR-T组患者的2年PFS率（65.52%）显著高于CAR-T组患者（30.00%，P = 0.0321）和CIT组患者（23.53%，P = 0.0043）。我们的结果支持CAR-T细胞疗法用于R/R中枢神经系统淋巴瘤的治疗。鉴于缓解的持久性和低毒性，ASCT联合CAR-T细胞疗法似乎是原发性和继发性R/R中枢神经系统淋巴瘤更有效、更安全的治疗选择。
