[Cellular kinetics and outcome of tisagenlecleucel for diffuse large B-cell lymphoma].

Ryo Hanajiri, Katsuya Furukawa, Marie Nakashima, Yoko Ushijima, Kazuyuki Shimada, Yuichi Ishikawa, Seitaro Terakura, Makoto Murata, Hitoshi Kiyoi
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Abstract

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.

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[弥漫性大b细胞淋巴瘤的细胞动力学和tisagenleclear的预后]。
靶向cd19的嵌合抗原受体t细胞(CAR-T)疗法已显示出治疗复发或难治性b细胞恶性肿瘤的希望。然而,输注后1个月内早期CAR-T监测的临床应用尚未阐明。在这项研究中,我们使用流式细胞术和定量聚合酶链反应定量测量了13例经组织细胞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2、4、7、9、11、14、21和28天的外周血CAR-T动力学。未发现整体CAR-T动力学与治疗结果之间的关系。有趣的是,应答者的CD4+ CAR-T扩增幅度高于无应答者,而应答者的CD8+ CAR-T扩增幅度最小。此外,CAR-T增殖在细胞因子释放综合征患者中更为明显。我们的研究结果表明,CAR-T输注后1个月内的CD4+ CAR-T细胞动力学可以预测成年DLBCL患者组织细胞治疗后的疗效。
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