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:Outcomes of loncastuximab tesirine in heavily pretreated patients with diffuse large B-cell lymphoma, including the post-CAR T-cell therapy setting: A meta-analysis.
Loncastuximab tesirine 在经重度治疗的 R/R DLBCL 中显示出具有临床意义的活性,包括 CAR-T 细胞治疗后的情形,血细胞减少常见但可控。汇总估计显示存在显著异质性,主要由真实世界队列驱动,应谨慎解读。
loncastuximab tesirine 是一种靶向 CD19 的抗体药物偶联物,用于治疗复发/难治性弥漫性大 B 细胞淋巴瘤(DLBCL),包括接受CAR-T 细胞治疗后的患者。本研究汇总了已发表队列中的疗效和安全性。
作者开展了一项关于 loncastuximab tesirine 单药治疗成人复发或难治性 DLBCL 的系统评价与 meta 分析。他们检索了 PubMed、Embase 和 Cochrane Library(自建库至 2025 年 10 月 25 日),以及美国血液学会 2025 年摘要。他们采用 Freeman-Tukey 转换的随机效应比例 meta 分析合并单臂比例,并从 Kaplan-Meier 曲线重建个体患者数据以进行时间-事件结局的合并(方案:PROSPERO CRD420251156779)。7 项研究(596 例患者)符合纳入标准。
七项研究(596 例患者)为所有分析中的临床结局提供了数据。汇总的总体缓解率为 45.76%(95% CI,28.75-63.28;I² = 94.3%),完全缓解率为 18.83%(95% CI,10.60-28.70;I² = 85.5%)。重建数据得出的汇总中位 PFS 为 5.18 个月(95% CI,3.97-6.15),中位 OS 为 9.01 个月(95% CI,7.60-10.73;四项研究)。在缓解者中,中位缓解持续时间为 10.22 个月(95% CI,6.37-不可估计)。3 级血小板减少、中性粒细胞减少和贫血的发生率分别为 23.71%、18.80% 和 11.01%,因不良事件而终止治疗的发生率为 12.61%(95% CI,5.85-21.18)。
BACKGROUND: Loncastuximab tesirine, a CD19-directed antibody-drug conjugate, is a therapy for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), including after chimeric antigen receptor T-cell therapy. This study summarized efficacy and safety across published cohorts. METHODS: The authors did a systematic review and meta-analysis of loncastuximab tesirine monotherapy in adults with relapsed or refractory DLBCL. They searched PubMed, Embase, and the Cochrane Library from inception to October 25, 2025, plus American Society of Hematology 2025 abstracts. They pooled single-arm proportions using random-effects proportional meta-analyses with Freeman-Tukey transformation and reconstructed individual patient data from Kaplan-Meier curves for time-to-event pooling (protocol: PROSPERO CRD420251156779). Seven studies (596 patients) met inclusion criteria. RESULTS: Seven studies (596 patients) contributed to clinical outcomes across all analyses. Pooled overall response was 45.76% (95% CI, 28.75-63.28; I 2 = 94.3%), and the complete response was 18.83% (95% CI, 10.60-28.70, I 2 = 85.5%). Reconstructed data yielded a pooled median progression-free survival of 5.18 months (95% CI, 3.97-6.15) and median overall survival was 9.01 months (95% CI, 7.60-10.73; four studies). Among responders, median duration of response was 10.22 months (95% CI, 6.37-not estimable). Grade 3 thrombocytopenia, neutropenia and anemia occurred in 23.71%, 18.80%, and 11.01% of patients, respectively, and treatment discontinuation due to adverse events occurred in 12.61% (95% CI, 5.85-21.18). CONCLUSIONS: Loncastuximab tesirine shows clinically meaningful activity in heavily pretreated R/R DLBCL, including post-CAR T-cell therapy settings, with frequent but manageable cytopenias. Pooled estimates showed substantial heterogeneity, driven mainly by real-world cohorts, and should be interpreted with caution.
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