决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Response kinetics following CAR T-cell therapy for large B-cell lymphoma: a LYSA study from the DESCAR-T registry.
M1 处的不完整响应不应自动提示观察并等待。
CAR T 细胞治疗后的缓解动力学仍特征不明。在这项使用法国 DESCAR-T 登记处(NCT04328298)的全国性真实世界证据研究中,我们分析了 1542 例既往接受过 2 种治疗后接受 CAR T 细胞治疗的大 B 细胞淋巴瘤成人患者的结局。在 1 个月(M1)时,49.1% 达到完全缓解(CR),28.9% 部分缓解(PR),6.1% 疾病稳定(SD),15.9% 疾病进展。M1 时中位无事件生存期(EFS)在 CR、PR 和 SD 患者中分别为 22.3、3.5 和 2.3 个月(p < 0.001)。在 484 例 M1 时不完全缓解(PR/SD)的患者中,35.5% 随后转为 CR,大多在 6 个月内。这些转化患者的缓解持续时间和总生存期(OS)与持续早期 CR 相当。多因素分析确定年龄 >65 岁、对桥接治疗无反应以及使用 tisagenlecleucel 是 CR 转化率较低、EFS 较短和 OS 降低的独立预测因素。结合这些因素的预后评分将 PR/SD 患者分层为四个结局不同的风险组。总之,M1 时不完全缓解不应自动采取观察等待。尽管超过三分之一转为 CR 且结局良好,但大多数进展或死亡,可能需要早期干预。这些发现支持风险适应性的输注后管理,并为未来前瞻性试验提供信息。临床试验注册:DESCAR-T 登记处注册于 ClinicalTrials.gov,标识符 NCT04328298。
Response kinetics after CAR T-cell therapy remain poorly characterized. In this nationwide real-world evidence study using the French DESCAR-T registry (NCT04328298), we analyzed outcomes in 1542 adults with large B-cell lymphoma treated with CAR T cells after 2 prior therapies. At one month (M1), 49.1% achieved complete remission (CR), 28.9% partial response (PR), 6.1% stable disease (SD), and 15.9% progressive disease. Median event-free survival (EFS) at M1 was 22.3 months for CR, 3.5 for PR, and 2.3 for SD (p < 0.001). Among 484 patients with incomplete response (PR/SD) at M1, 35.5% subsequently converted to CR, mostly within 6 months. These conversions were associated with response duration and overall survival (OS) comparable to sustained early CR. Multivariate analyses identified age >65 years, lack of response to bridging therapy, and tisagenlecleucel use as independent predictors of lower CR conversion, shorter EFS, and reduced OS. A prognostic score combining these factors stratified PR/SD patients into four risk groups with distinct outcomes. In conclusion, an incomplete response at M1 should not automatically prompt watch-and-wait. Although over one-third convert to CR with favorable outcomes, most progress or die and may require early intervention. These findings support risk-adapted post-infusion management and inform future prospective trials. CLINICAL TRIAL REGISTRATION: The DESCAR-T registry is registered under ClinicalTrials.gov identifier NCT04328298.
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