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CAR-T 细胞治疗失败并暴露于双特异性抗体后的异基因移植:可行性、安全性与生存结局

英文原题:Allogeneic transplantation after failure of chimeric antigen receptor-T cells and exposure to bispecific antibodies: Feasibility, safety and survival outcomes.

查看英文原题

Allogeneic transplantation after failure of chimeric antigen receptor-T cells and exposure to bispecific antibodies: Feasibility, safety and survival outcomes.

PubMed 2025/07/22(内容时间) Br J Haematol Q2 · IF 3.6(JCR 2025)

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中文摘要

大B细胞淋巴瘤(LBCL)患者在接受嵌合抗原受体(CAR)-T细胞治疗失败后,临床结局不容乐观。异基因干细胞移植(alloSCT)是复发/难治性LBCL的一种潜在治愈性挽救治疗,尽管对于曾接受CAR-T 和双特异性抗体治疗的患者,其可行性和安全性仍存在担忧。2019年至2025年间,在两个学术中心接受CAR-T 治疗的170例LBCL患者中,记录了83例疾病进展;69例(83%)开始了挽救治疗,其中最常用的是glofitamab,38例(55%);在这些患者中,我们回顾性分析了35例适合alloSCT巩固治疗候选者的结局。最终,13例(37%)在达到完全缓解(CR)或部分缓解后接受了alloSCT。既往治疗的中位线数为5。所有患者均成功植入;III-IV级急性移植物抗宿主病(GvHD)发生率为8%,中重度慢性GvHD发生率分别为15%。在中位随访18.4个月时,非复发死亡率为0%;所有接受异基因移植的患者均存活且处于CR;相反,22例未进行移植的患者结局较差,中位总生存期为11.7个月,13例疾病相关死亡(59%)。尽管患者队列较小,我们的数据强调了alloSCT巩固治疗对挽救方案选定应答者的潜在获益,尽管这些患者既往接受了大量的T细胞重定向治疗。

展开英文摘要原文

Clinical outcome after chimeric antigen receptor (CAR)-T-cell failure in large B-cell lymphoma (LBCL) is dismal. Allogeneic stem cell transplantation (alloSCT) represents a potentially curative salvage for relapsed/refractory LBCL, although concerns remain regarding its feasibility and safety in patients exposed to CAR-T and bispecific antibodies. Between 2019 and 2025, 83 disease progressions were documented among 170 LBCL patients treated with CAR-T in two academic centres; 69 (83%) started salvage treatment, the most frequent being glofitamab in 38 (55%); among those, we retrospectively analysed outcomes of 35 candidates for alloSCT consolidation. Ultimately, 13 (37%) underwent alloSCT after achieving complete (CR) or partial response.

The median number of previous therapies was 5. All patients engrafted; grade III-IV acute graft-versus-host disease (GvHD) occurred in 8% and moderate-to-severe chronic GvHD in 15% of patients respectively. At 18. 4-month median follow-up, non-relapse mortality was 0%; all allografted patients are alive in CR; conversely, the outcome of 22 patients not proceeding to transplant was poor, with a median overall survival of 11.

7 months and 13 disease-related deaths (59%). Although in a small cohort of patients, our data highlight the potential benefit of alloSCT consolidation in selected responders to salvage regimens despite the extensive prior treatments with T-cell redirecting therapies.

论文信息

作者
Barone A、De Philippis C、Stella F、Dodero A、Sarina B、Pennisi M、Santoro A、Carlo-Stella C
单位
University of Milan, Milan, Italy.Italy
文献类型
多中心研究
期刊
British journal of haematology2025 Sep
原文标识
PubMed 40695357 · DOI 10.1111/bjh.70010