淋巴细胞清除化疗 (LDC) 对于 CAR T 细胞扩增和疗效至关重要。尽管如此，文献中对于最佳 LDC 治疗方案（包括剂量和频率）尚未达成共识。我们回顾性地回顾性地评价了单个机构的连续患者，这些患者在使用 CD19 定向 CAR T 细胞产品 axicabtagene ciloleucel 和 tisagenlecleucel 治疗之前接受了 LDC 。在2019年5月之前，在我们中心接受治疗的患者连续3天接受氟达拉滨30 mg/m2和环磷酰胺500 mg/m2。在此时间点之后，患者常规接受连续2天氟达拉滨40 mg/m2和环磷酰胺500 mg/m2。从电子病历中获取每个队列的临床数据，并比较 CAR T 细胞疗效和毒性的差异。从 2018 年 6 月到 2023 年 8 月，在 CD19 定向 CAR T 细胞治疗复发性非复发性癌症之前，对 92 名患者进行了 LDC 治疗。 - 霍奇金淋巴瘤。 28 名患者接受了 3 天的治疗方案，64 名患者接受了 2 天的治疗方案。在整个队列中，75% 的患者接受 axicabtagene ciloleucel，25% 的患者接受 tisagenlecleucel。 2 天治疗组和 3 天治疗组的总体缓解率相似（69% vs 75%，p = 0.21），完全缓解率也相似（50% vs 54%，p = 0.82）。 2-4 级细胞因子释放综合征（55% vs 50%，p=0.82）、2-4 级免疫效应细胞相关神经毒性综合征（42% vs 29%，p=0.25），或中性粒细胞减少症或血小板减少症缓解的时间。 3 天治疗方案的血小板恢复时间持续超过 60 天的比例更高（9% vs 27%，p=0.026）。随着符合 CAR T 细胞治疗资格的患者数量持续增加，优化每个组成部分的治疗是必要的。我们证明，使用氟达拉滨和环磷酰胺进行为期 2 天的 LDC 治疗方案是可行的，不会对 CAR T 细胞功效或毒性产生显着影响。有必要进行前瞻性研究以进一步确定最有效的 LDC 治疗方案。版权所有 © 2024 Frame, Geer, Kasha, Markstrom, Scappaticci, Feeney, Hayduk, Mansoor, Oberfeld, D'Antonio, Anand, Choi, Maciejewski, Pawarode, Riwes, Tewari,马格诺和戈什。

Lymphodepleting chemotherapy (LDC) is critical to CAR T-cell expansion and efficacy. Despite this, there is not a consensus in the literature regarding the optimal LDC regimen, including dose and frequency.We retrospectively reviewed consecutive patients at a single institution that received LDC prior to treatment with the CD19 directed CAR T-cell products axicabtagene ciloleucel and tisagenlecleucel. Patients treated at our center received fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 consecutive days prior to May 2019. After this timepoint patients routinely received fludarabine 40 mg/m2 and cyclophosphamide 500 mg/m2 for 2 consecutive days. Clinical data from each cohort were obtained from the electronic medical record and compared for differences in CAR T-cell efficacy and toxicity.From June 2018 to August 2023, LDC was given to 92 patients prior to CD19 directed CAR T-cell therapy for relapsed non-Hodgkin's lymphoma. Twenty-eight patients received a 3-day regimen, and 64 patients received a 2-day regimen. In the total cohort, 75% of patients received axicabtagene ciloleucel and 25% received tisagenlecleucel. The overall response rates in both the 2-day regimen group and the 3-day regimen group were similar (69% vs 75%, p= 0.21) as were the complete response rates (50% vs 54%, p=0.82). There were no significant differences between the 2-day and 3-day regimens for grade 2-4 cytokine release syndrome (55% vs 50%, p=0.82), grade 2-4 immune effector cell associated-neurotoxicity syndrome (42% vs 29%, p=0.25), or time to resolution of neutropenia or thrombocytopenia. The rate of prolonged platelet recovery lasting greater than 60 days was higher with the 3-day regimen (9% vs 27%, p=0.026).As the number of patients eligible for CAR T-cell therapy continues to increase, optimizing each component of therapy is necessary. We show that a 2-day regimen of LDC with fludarabine and cyclophosphamide is feasible without significant impact on CAR T-cell efficacy or toxicity. Prospective studies are necessary to further determine the most effective LDC regimen.Copyright © 2024 Frame, Geer, Kasha, Markstrom, Scappaticci, Feeney, Hayduk, Mansoor, Oberfeld, D’Antonio, Anand, Choi, Maciejewski, Pawarode, Riwes, Tewari, Magenau and Ghosh.