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:Clinical significance of complete remission and measurable residual disease in relapsed/refractory multiple myeloma patients treated with T-cell redirecting immunotherapy.
Clinical significance of complete remission and measurable residual disease in relapsed/refractory multiple myeloma patients treated with T-cell redirecting immunotherapy.
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接受T细胞重定向免疫疗法的复发/难治性多发性骨髓瘤(RRMM)患者中,可测量残留病(MRD)的影响尚不确定。我们对201例临床试验患者开展新一代流式细胞术分析,研究接受嵌合抗原受体(CAR)T细胞或T细胞衔接器(TCE)治疗后的MRD动态。在10^-6阈值达到MRD阴性与疾病进展和/或死亡风险降低89%相关。与MRD阴性短暂的患者相比,持续MRD阴性患者生存结局改善;持续MRD阳性患者的结局则很差。意向治疗分析中,CAR-T 细胞治疗患者的MRD阴性率高于TCE治疗患者。
然而,在达到MRD阴性的患者中,按CAR-T 细胞或TCE治疗分层后,生存结局无差异。多变量分析纳入既往治疗线数、国际分期系统、细胞遗传学风险、髓外疾病和T细胞重定向免疫疗法类型;只有完全缓解(CR)和MRD状态对无进展生存期和总生存期具有独立预后价值。
总之,本研究显示,深度且持续的MRD阴性CR是最重要的预后因素,应作为CAR-T 细胞和TCE治疗RRMM患者的治疗终点。
The impact of measurable residual disease (MRD) in relapse/refractory multiple myeloma (RRMM) patients treated with T-cell redirecting immunotherapy is uncertain.
We analyzed MRD dynamics using next-generation flow in 201 patients treated in clinical trials with chimeric antigen receptor (CAR) T cells and T-cell engagers (TCE). Achieving MRD negativity at 10 -6 was associated with 89% reduction in the risk of progression and/or death. Survival outcomes were improved in patients with sustained versus transient MRD negativity and were dismal in those who remained MRD positive. The intent-to-treat MRD negative rates were higher in patients treated with CAR T cells versus TCE.
However, among patients achieving MRD negativity, there were no differences in survival outcomes when stratified according to treatment with CAR T cells versus TCE. In multivariate analysis including the number of prior lines of treatment, International Staging System, cytogenetic risk, extramedullary disease and type of T-cell redirecting immunotherapy, only the complete remission (CR) and MRD statuses showed independent prognostic value for progression-free and overall survival.
In conclusion, our study shows that deep and sustained MRD negative CR is the most relevant prognostic factor and should be considered as the treatment endpoint in RRMM patients treated with CAR T cells and TCE.
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