复发/难治性 (R/R) 中枢神经系统淋巴瘤 (CNSL) 与预后不良相关。 Relmacabtagene autoleucel (relma-cel) 表达与 lisocabtagene maraleucel 相同的嵌合抗原受体 (CAR)，采用中国开发的优化的商业化工艺，在关键 RELIANCE 研究中表现出显着的疗效和可控的安全性。然而，目前还没有关于 relma-cel“真实世界”使用的公开数据，特别是对于 CNS 受累的患者。对 12 个诊所用于 R/R CNSL 患者的商业 relma-cel 进行了回顾性分析。主要终点是评估 3 个月时达到完全缓解 (CR) 的患者比例。次要终点包括最佳完全缓解 (BCR)、无进展生存期 (PFS)、缓解持续时间 (DOR)、总生存期 (OS) 和不良事件发生率。 在 22 名 CNSL 患者中（12 名原发性 CNSL；10 名次要 CNSL） CNSLs），最佳总体缓解率为 90.9%，BCR 率为 68.2%。中位随访时间为 316 天（范围为 55-618 天），估计的 1 年 PFS 率、DOR 和 OS 率分别为 64.4%、71.5% 和 79.2%。在持久 CR 或对最近一次治疗前白细胞去除术部分缓解并接受 relma-cel 作为巩固治疗的患者中观察到显着的临床益处 (n=8)，1 年 PFS 率为 100.0% 对比 41.7% (p =0.02）。此外，就主要终点而言，输注后 3 个月的非 CR 似乎预示着较差的预后，估计的 1 年 PFS 分别为 83.3% 和 37.0% (p=0.03)。 72.9% 的患者发生 CRS（3 级：4.5%），36.4% 的患者发生免疫效应细胞相关神经毒性综合征（3 级：4.5%）。在正在进行的 BTKi 中添加附加剂 PD-1 抑制剂（替雷利珠单抗）后，中位 2 周（范围：12-32 天）后通过定量 PCR 或流式细胞术检测到 CAR T 细胞显着重新扩增。这项研究是商业 relma-cel 用于 R/R CNSL 的第一个也是最大的现实世界研究，证明了有希望的疗效和可接受的安全性。我们重申了 BTKi 或 PD-1 抑制剂等免疫制剂对 CAR T 细胞再扩增的益处，并假设了双药 CAR-T 相关组合疗法，值得进一步验证。最重要的是，我们强调了早期使用 CAR T 细胞疗法作为对挽救疗法敏感的患者的巩固疗法，这提供了动力和启发未来的策略。© 作者（或其雇主）2024。 CC BY-NC 允许重复使用。禁止商业再利用。请参阅权利和权限。英国医学杂志出版。

Relapsed/refractory (R/R) central nervous system lymphomas (CNSLs) are associated with a poor prognosis. Relmacabtagene autoleucel (relma-cel), expressing the same chimeric antigen receptor (CAR) as lisocabtagene maraleucel, with an optimized commercial-ready process developed in China, demonstrated remarkable efficacy and manageable safety in the pivotal RELIANCE study. However, no published data are available on the "real-world" use of relma-cel, especially for patients with CNS involvement.Retrospective analyses were conducted for commercial relma-cel used in patients with R/R CNSL at 12 clinics. The primary endpoint was to evaluate the proportion of patients who achieved complete response (CR) at 3 months. Secondary endpoints included best complete response (BCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and the incidence of adverse events.Among the 22 CNSL patients (12 primary CNSLs; 10 secondary CNSLs), the best overall response rate was 90.9% and the BCR rate was 68.2%. With median follow-up of 316 days (range, 55-618 days), the estimated 1-year PFS rate, DOR, and OS rate were 64.4%, 71.5%, and 79.2%, respectively. Significant clinical benefits were observed in patients who were in durable CR or partial response to the most recent prior therapy preleukapheresis and received relma-cel as consolidation therapy (n=8), with 1-year PFS rate of 100.0% versus 41.7% (p=0.02). In addition, in terms of primary endpoint, non-CR at 3 months postinfusion seemed to be predictive of a worse prognosis, with an estimated 1-year PFS of 83.3% versus 37.0% (p=0.03), respectively. CRS occurred in 72.9% of patients (grade 3: 4.5%) and immune effector cell-associated neurotoxicity syndrome in 36.4% of patients (grade 3: 4.5%). With the add-on agent PD-1 inhibitor (tislelizumab) to the ongoing BTKi, significant re-expansions of CAR T-cell were detected by quantitative PCR or flow cytometry after a median of 2 weeks (range, 12-32 days).This study was the first and largest real-world study of commercial relma-cel for R/R CNSL, demonstrating promising efficacy and acceptable safety. We reaffirmed the benefit of immuno-agents such as BTKi or PD-1 inhibitor on CAR T-cell re-expansion and hypothesized a dual-agent CAR-T related combinatorial therapies, which warrants further validation. Most importantly, we highlighted the earlier use of CAR T-cell therapy as a consolidative therapy for patients sensitive to salvage therapy, which provided an impetus and inspired-future strategy.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.