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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Be cautious to adopt a second CAR T-cell infusion after failure of CD19/CD22 cocktail CAR T-cell therapy in relapsed/refractory B-NHL.
Be cautious to adopt a second CAR T-cell infusion after failure of CD19/CD22 cocktail CAR T-cell therapy in relapsed/refractory B-NHL.
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嵌合抗原受体(CAR)T 细胞输注(CTI)疗法已成为复发/难治性 B 细胞非霍奇金淋巴瘤(R/R B-NHL)的突破性疗法,但仍有相当数量患者治疗失败。首次 CTI(CTI1)失败后患者的疾病史、后续挽救治疗和结局,尚未得到详细报告或系统研究。
本研究回顾性分析了 CTI1 治疗失败后接受挽救治疗的 61 例 R/R B-NHL 患者,详细描述其临床特征、后续管理和结局。结果提示,少数患者在 CTI1 失败后接受第二次 CTI(CTI2)挽救治疗,其短期总体缓解率高于其他挽救治疗(非 CTI2):8/27 对 2/34,P = 0.014。
然而,非 CTI2 组的无事件生存期(EFS,P = 0.007)和总生存期(OS,P = 0.048)优于 CTI2 组,中位随访分别为 6.7 个月和 4.7 个月。单变量和多变量分析均显示,只有疾病起病时的肿瘤状态是生存的独立危险因素;CTI1 失败后的挽救治疗方式不是独立危险因素。CTI2 治疗的不良反应总体与非 CTI2 治疗相似,但感染相关死亡明显更多。
总之,无论后续采用何种挽救治疗,CTI1 失败患者的预后都很差;对于接受 CD19/22 双靶点 CTI1 后治疗失败的 R/R B-NHL 患者,临床医生应谨慎考虑 CTI2。仍需开展大规模前瞻性研究,迫切需要新策略来预防治疗失败并改善 B 细胞淋巴瘤患者生存。
Chimeric antigen receptor (CAR) T-cell infusion (CTI) therapy has emerged as a breakthrough therapy in relapsed/refractory B-cell non-Hodgkin's lymphoma (R/R B-NHL), but a substantial number of patients still suffer treatment failure. Data on disease history, subsequent salvage therapies, and outcomes of patients who face treatment failure after the first CTI (CTI1) have not been reported in detail or systematically studied.
Here, a retrospective analysis was performed on a total of 61 R/R B-NHL patients in whom salvage therapies were adopted after CTI1 treatment failure, with their clinical characteristics, subsequent management and outcomes described in detail.
The results suggested that second-time CTI (CTI2) used as salvage therapy after failure of CTI1 could achieve a better transient overall response rate (ORR) than other salvage treatments (non-CTI2) in only a minority of patients (8/27 vs. 2/34, P=0. 014). Nevertheless, the non-CTI2 group showed better event-free survival (EFS) (P = 0. 007) and overall survival (OS) (P = 0. 048) than the CTI2 group, with a median follow-up of 6. 7 months vs. 4. 7 months.
In addition, univariate and multivariate analyses showed that only the status of the tumor at disease onset was an independent risk factor for survival; salvage therapy after CTI1 treatment failure was not. The adverse effects of CTI2 treatment were generally similar to those of non-CTI2 treatment, but the infection-related mortality was considerably higher.
In conclusion, the prognosis of patients who fail CTI1 therapy is very poor regardless of the subsequent salvage therapies, and clinicians should be cautious about adopting CTI2 treatment after failure of treatment with the CD19/22 cocktail CTI1 in R/R B-NHL. Large-scale prospective studies are warranted, and new strategies are urgently needed to prevent treatment failure and improve the survival of B-cell lymphoma patients in future.
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