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Blood:既可缓解CD19 CAR T细胞细胞因子释放综合征,又不减弱抗白血病疗效

2019-10-15 QQY MedSci原创

采用CD19特异性嵌合抗原受体重定向的T细胞适配性转移的免疫疗法治疗B系急性淋巴细胞白血病,可挽救80%以上的复发性/难治性疾病患者。这种新形式的治疗指数由于CAR T细胞移植时出现的免疫毒性综合征而降低。

中心点:

早期应用托珠单抗和类固醇并不影响B-ALL中SCRI-CAR19v1 CAR T细胞的扩增或持续存在

注射托珠单抗和糖皮质激素并不负性影响SCRI-CAR19v1的疗效

摘要:

采用CD19特异性嵌合抗原受体重定向的T细胞适配性转移的免疫疗法治疗B系急性淋巴细胞白血病,可挽救80%以上的复发性/难治性疾病患者。这种新形式的治疗指数由于CAR T细胞移植时出现的免疫毒性综合征而降低。

近期,研究人员发现在接受CD4:CD8 T细胞成分4-1BB:ζ CAR T细胞产品治疗的患者中,重度细胞因子释放综合征的发生率较低。而且早期注射托珠单抗和(或)糖皮质激素干预可能会降低受试者从轻度CRS向严重CRS转变的概率。

但虽然早期使用托西珠单抗和/或皮质类固醇干预的受试者的数量增加了一倍,但与未接受干预的受试者相比,对最小残留病灶阴性完全缓解率或随后的功能性CAR T细胞的持久性,均无明显的有害影响。此外,早期予以干预措施并没有增加神经毒性或感染后后遗症的风险。

综上所述,本研究数据支持对有早期CRS症状的受试者,予以托珠单抗和糖皮质激素干预,而且不负性影响CD19CAR T细胞的抗肿瘤特性。这干预措施有望提高复发性/难治性患者的治疗指数,并为CAR T细胞治疗在ALL治疗中更广泛地应用提供了理论基础。

原始出处:

Rebecca Gardner, et al.Preemptive Mitigation of CD19 CAR T Cell Cytokine Release Syndrome Without Attenuation of Anti-Leukemic Efficacy .Blood .2019001463. https://doi.org/10.1182/blood.2019001463

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    2019-10-17 dingxiaobo
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    2019-10-16 内科新手

    谢谢梅斯提供这么好的信息,学到很多

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大剂量化疗后进行自体干细胞移植(HDT-ASCT)是复发性或化疗难治性弥漫性大B细胞淋巴瘤(rel/ref DLBCL)的标准疗法。但只有50%的患者用这种方法治愈。HDT-ASCT后予以CD19特异性嵌合抗原受体(CAR) T细胞是否可以提高患者的无进展存活期 (PFS)? Craig S. Sauter等人对此进行研究。

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