CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Allogeneic transplantation after failure of chimeric antigen receptor-T cells and exposure to bispecific antibodies: Feasibility, safety and survival outcomes.
Allogeneic transplantation after failure of chimeric antigen receptor-T cells and exposure to bispecific antibodies: Feasibility, safety and survival outcomes.
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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。
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.
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