Cellular kinetics and outcome of tisagenlecleucel for diffuse large B-cell lymphoma
Cellular kinetics and outcome of tisagenlecleucel for diffuse large B-cell lymphoma
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tisagenlecleucel 治疗弥漫性大 B 细胞淋巴瘤的细胞动力学和结果
DOI：
10.11406/rinketsu.64.167
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
清井 仁
中科院分区：
文献类型：
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作者：
葉名尻 良;古川 勝也;中島 麻梨絵;牛島 洋子;島田 和之;石川 裕一;寺倉 精太郎;村田 誠;清井 仁
CD19 靶向嵌合抗原受体 T 细胞 (CAR-T) 疗法已显示出治疗复发或难治性 B 细胞恶性肿瘤的前景。然而，输注后1个月内早期CAR-T监测的临床效用尚未阐明。在这项研究中，我们使用流式细胞术和定量聚合酶链反应对 13 名接受 tisagenlecleucel (tisa-cel) 治疗的复发难治性弥漫性大 B 细胞淋巴瘤 (DLBCL) 患者在输注后第 2、4、7、9、11、14、21 和 28 天的外周血中的 CAR-T 动力学进行了定量测量。未发现批量 CAR-T 动力学与治疗结果之间存在任何关系。有趣的是，应答者中 CD4+ CAR-T 扩增的程度高于无应答者，而应答者中 CD8+ CAR-T 扩增的程度最小。此外，CAR-T 增殖在细胞因子释放综合征患者中更为明显。我们的结果表明，CAR-T 输注后 1 个月内的 CD4+ CAR-T 细胞动力学可以预测其在成人 DLBCL 患者中接受 tisa-cel 治疗后的疗效。
CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promise as treatment of relapsed or refractory B-cell malignancies. However, the clinical utility of early CAR-T monitoring within 1 month after infusion has not been elucidated. In this study, we quantitatively measured CAR-T kinetics in peripheral blood on days 2, 4, 7, 9, 11, 14, 21, and 28 post-infusion using flow cytometry and quantitative polymerase chain reaction in 13 patients with relapsed refractory diffuse large B-cell lymphoma (DLBCL) treated with tisagenlecleucel (tisa-cel). No relationships were identified between bulk CAR-T kinetics and treatment outcomes. Interestingly, the magnitude of CD4+ CAR-T expansion was higher in responders than in nonresponders, while CD8+ CAR-T expansion was minimal in responders. Additionally, CAR-T proliferation was more pronounced in patients with cytokine release syndrome. Our results suggest that CD4+ CAR-T cellular kinetics within 1 month after CAR-T infusion may predict its efficacy after tisa-cel therapy in adult patients with DLBCL.