Blood:CD19 CAR-T细胞疗法明显提高ALL患者的无事件存活期

2019-02-09 MedSci MedSci原创

中心点:基础血小板计数、LDH和淋巴细胞耗竭方案均会影响CD19 CAR-T细胞治疗后获得MRD阴性的完全缓解的患者的无事件存活期。CD19 CAR-T细胞治疗后进行同种异体HCT,患者耐受性好,还有望延长患者的无事件存活期。摘要:特异性表达CD19嵌合抗原受体(CAR)的自体T细胞可提高复发性/难治性急性B淋巴细胞白血病(B-ALL)患者的微小残留病阴性的完全缓解(MRD-CR)率。但是,与CA

中心点:

基础血小板计数、LDH和淋巴细胞耗竭方案均会影响CD19 CAR-T细胞治疗后获得MRD阴性的完全缓解的患者的无事件存活期。

CD19 CAR-T细胞治疗后进行同种异体HCT,患者耐受性好,还有望延长患者的无事件存活期。

摘要:

特异性表达CD19嵌合抗原受体(CAR)的自体T细胞可提高复发性/难治性急性B淋巴细胞白血病(B-ALL)患者的微小残留病阴性的完全缓解(MRD-CR)率。但是,与CAR-T细胞治疗后持续缓解相关的细胞因子尚未完全明确。

Kevin A. Hay等人对参与评估淋巴细胞耗竭化疗后予以CD19 CAR-T细胞治疗的I/II期临床试验(NCT01865617)所有复发性/难治性B-ALL患者进行分析研究。53位接受CD19 CAR-T细胞治疗的患者中有45位(85%)获得MRD-阴性的完全缓解。

中位随访30.9个月,获得MRD阴性CR患者的无事件存活期(EFS)和总体存活期均明显长于非MRD阴性CR患者(中位EFS:7.6 vs 0.8个月,p<0.001;中位OS:20.0 vs 5.0个月,p=0.14)。对于MRD阴性CR患者,恶性克隆指数低(IGH深度测序)提示EFS较好(p=0.34)。对MRD阴性CR患者进行多变量模型分析显示,淋巴细胞耗竭前LDH浓度低(风险比[HR] 1.38/[每增加100U/L])、血小板计数较高(HR 0.74/[每升高50000/ul]),采用氟达拉滨进行淋巴细胞耗竭(HR 0.25)以及CAR-T细胞治疗后进行HCT(HR 0.39)均与EFS更高相关。

本研究数据有助于鉴别CAR-T细胞免疫疗法后高复发风险的患者,以便及时进行巩固治疗,如造血干细胞移植。


原始出处:

Kevin A. Hay,et al.Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR-T cells. Blood 2019 :blood-2018-11-883710; doi: https://doi.org/10.1182/blood-2018-11-883710 

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    2019-06-16 仁心济世
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    2019-02-11 膀胱癌
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    2019-02-11 dingxiaobo
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