J Clin Oncol:优化成人急性淋巴细胞白血病患者的嵌合抗原受体T细胞治疗

2020-09-30 MedSci原创 MedSci原创

抗CD19嵌合抗原受体T细胞疗法tisagenlecleucel(CTL019)在复发或化疗难治性(r/r)B细胞急性淋巴细胞白血病(ALL)儿童中的反应率为81%。细胞因子释放综合征(CRS)是一种

抗CD19嵌合抗原受体T细胞疗法tisagenlecleucel(CTL019)在复发或化疗难治性(r/r)B细胞急性淋巴细胞白血病(ALL)儿童中的反应率为81%。细胞因子释放综合征(CRS)是一种威胁生命的治疗相关毒性,限制了成人的全部治疗潜力。我们报告了采用优化的CTL019剂量和CRS管理策略治疗的r/r ALL成人的结果。

在2个试验中的1个试验中,r/r B细胞ALL的成人接受CTL019。患者接受淋巴结清扫术,随后CTL019以一次性输注或分次输注的方式分3天(第1天,10%;第2天,30%;第3天,60%)进行,这使得第2天和第3天的剂量用于早期CRS。计划的CTL019总剂量随着疗效和CRS毒性的适应性方案修改而变化。

 

结果显示,在所有三个给药组中,有35个r / r ALL的成年人接受了CTL019。低剂量队列(n = 9)接受单次或分次给药,毒性可控,完全缓解(CR)率为33%。在高剂量单次输注队列中,6名难治性CRS同时伴有培养阳性脓毒症的患者中有3人死亡,3人获得CR。高剂量分次(HDF)队列中的20名患者CR率为90%,CRS可控。HDF队列的生存率最高,2年总生存率为73%(95% CI,46%~88%),无事件生存率为49.5%(95% CI,21%~73%)。

 

综上所述,该研究结果表明,CTL019的分次给药与患者内剂量调整优化了成人r/r ALL的安全性而不影响疗效。

 

原始出处:

 

Noelle V FreyPamela A Shaw, et al., Optimizing Chimeric Antigen Receptor T-Cell Therapy for Adults With Acute Lymphoblastic Leukemia. J Clin Oncol. 2020 Feb 10;38(5):415-422. doi: 10.1200/JCO.19.01892. 

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    2020-10-01 anti-cancer

    谢谢梅斯分享这么多精彩信息

    0

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中心点:间充质干细胞可以转化成癌相关的成纤维细胞,并转移线粒体,从而将B-ALL细胞从ROS诱导的化疗中拯救出来。B-ALL细胞的拯救是通过微管抑制剂来完成的,微管抑制剂可阻断用于线粒体转移的隧道化纳米管。摘要:Burt等人对成人急性淋巴细胞白血病(ALL)间充质干细胞(MSC)壁龛进行研究和建模。研究人员使用基因表达谱、细胞因子/趋化因子定量、流式细胞术和多种成像技术发现,直接从ALL患者的原始

Blood:亚克隆NT5C2突变与急性淋巴细胞白血病复发后的预后不良的相关性

胞质5'-核苷酸酶II (NT5C2)的激活突变被认为通过赋予嘌呤类似物耐受性来驱动急性淋巴细胞白血病(ALL)的复发。为了检验NT5C2突变对ALL复发患者的临床作用,Malwine J Barz等人采用测序和敏感等位基因特异性RT-PCR分析了455例在ALL-REZ BFM 2002复发试验中治疗的复发性B细胞前体ALL患者的NT5C2基因。研究人员在75例(75/455,16.5%)复发性