CD19-directed chimeric antigen receptor T (CAR-T) cells have been widely reported in the therapy of relapsed/refractory non-Hodgkin lymphoma (NHL). Both cryopreserved and fresh formulations of CAR-T have been used in previous studies. However, quite a few studies investigated the effects of cryopreservation on the clinical outcomes of CAR-T cells. Here we retrospectively analyzed a phase I/II clinical trial of CD19-directed CAR-T cells in NHL patients, and compared the safety and efficacy of cryopreserved and fresh CAR-T products. All CAR-T cells were prepared using the same manufacturing process except the formulation step. Fifteen patients were infused with cryopreserved/thawed CAR-T cells, and 8 patients were treated with fresh CAR-T cells. Comparative overall response rates and in vivo expansion kinetics of CAR-T cells were observed between the cryopreserved cohort and fresh cohort. The occurrence rates of cytokine release syndrome and neurotoxicity were also similar in both groups. Patients in the fresh cohort showed higher incidence of acute hematological toxicity including anemia, hypoleukemia, and thrombocytopenia. This study demonstrated that cryopreservation showed negligible effects on the efficacy of CD19-directed CAR-T cells, but endowed CAR-T cells with higher safety in NHL patients, supporting the application of cryopreserved CAR-T products for NHL therapy.

中文翻译：

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新鲜与冷冻保存的 CD19 定向嵌合抗原受体 T 细胞在非霍奇金淋巴瘤患者中的临床结果

CD19 定向嵌合抗原受体 T (CAR-T) 细胞已被广泛报道用于治疗复发/难治性非霍奇金淋巴瘤 (NHL)。CAR-T 的冷冻保存和新鲜制剂均已用于之前的研究。然而，相当多的研究调查了冷冻保存对 CAR-T 细胞临床结果的影响。在这里，我们回顾性分析了 NHL 患者中 CD19 导向的 CAR-T 细胞的 I/II 期临床试验，并比较了冷冻保存和新鲜 CAR-T 产品的安全性和有效性。除配方步骤外，所有 CAR-T 细胞均使用相同的制造工艺制备。15 名患者输注了冷冻/解冻的 CAR-T 细胞，8 名患者接受了新鲜的 CAR-T 细胞治疗。在冷冻保存的队列和新鲜的队列之间观察到 CAR-T 细胞的总体反应率和体内扩增动力学的比较。两组细胞因子释放综合征和神经毒性的发生率也相似。新队列中的患者显示出较高的急性血液学毒性，包括贫血、低白血病和血小板减少症。本研究表明，冷冻保存对CD19导向的CAR-T细胞的疗效影响微乎其微，但赋予CAR-T细胞在NHL患者中更高的安全性，支持冷冻保存的CAR-T产品在NHL治疗中的应用。新队列中的患者显示出较高的急性血液学毒性，包括贫血、低白血病和血小板减少症。本研究表明，冷冻保存对CD19导向的CAR-T细胞的疗效影响微乎其微，但赋予CAR-T细胞在NHL患者中更高的安全性，支持冷冻保存的CAR-T产品在NHL治疗中的应用。新队列中的患者显示出较高的急性血液学毒性，包括贫血、低白血病和血小板减少症。本研究表明，冷冻保存对CD19导向的CAR-T细胞的疗效影响微乎其微，但赋予CAR-T细胞在NHL患者中更高的安全性，支持冷冻保存的CAR-T产品在NHL治疗中的应用。