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[替沙格赛定用于弥漫性大B细胞淋巴瘤的细胞动力学及疗效]

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

作者信息

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

机构信息

Department of Hematology, Nagoya University Hospital.

出版信息

Rinsho Ketsueki. 2023;64(3):167-174. doi: 10.11406/rinketsu.64.167.

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.

摘要

靶向CD19的嵌合抗原受体T细胞(CAR-T)疗法已显示出有望用于治疗复发或难治性B细胞恶性肿瘤。然而,输注后1个月内早期CAR-T监测的临床效用尚未阐明。在本研究中,我们使用流式细胞术和定量聚合酶链反应,对13例接受替沙格韦单抗(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CAR-T动力学进行了定量测量。未发现总体CAR-T动力学与治疗结果之间存在关联。有趣的是,反应者中CD4 CAR-T扩增的幅度高于无反应者,而反应者中CD8 CAR-T扩增最小。此外,细胞因子释放综合征患者的CAR-T增殖更为明显。我们的结果表明,CAR-T输注后1个月内的CD4 CAR-T细胞动力学可能预测tisa-cel治疗成年DLBCL患者后的疗效。

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