PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
摘要：
■淋巴消耗化疗（LDC）对于CAR-T细胞扩增和疗效至关重要。尽管如此,关于最不发达国家的最佳方案，文献中没有达成共识，包括剂量和频率。
■我们回顾性分析了在使用CD19定向CAR-T细胞产物axicabtageneciloleucel和tisagenlecleucel治疗之前接受LDC的单个机构的连续患者。在我们中心治疗的患者在2019年5月之前连续3天接受氟达拉滨30mg/m2和环磷酰胺500mg/m2。在该时间点之后,患者常规地接受氟达拉滨40mg/m2和环磷酰胺500mg/m2连续2天。从电子病历中获得每个队列的临床数据，并比较CART细胞功效和毒性的差异。
■从2018年6月至2023年8月，在接受CD19定向CART细胞治疗复发性非霍奇金淋巴瘤之前，对92名患者进行了LDC治疗。28名患者接受了为期3天的治疗方案，64例患者接受了2天的治疗方案。在总队列中，75％的患者接受了axicabtageneciloleucel，25％的患者接受了tisagenlecleucel。2天方案组和3天方案组的总反应率相似(69%vs75%,p=0.21)以及完全缓解率(50%对54%，p=0.82）。2-4级细胞因子释放综合征的2天和3天方案之间没有显着差异（55％vs50％，p=0.82)，2-4级免疫效应细胞相关神经毒性综合征(42%vs29%，p=0.25),或中性粒细胞减少症或血小板减少症的消退时间。3天治疗方案的血小板恢复时间超过60天的比率更高(9%vs27%,p=0.026)。
■随着有资格接受CAR-T细胞治疗的患者数量不断增加，优化治疗的每个组成部分是必要的。我们表明，使用氟达拉滨和环磷酰胺的LDC2天方案是可行的，对CART细胞功效或毒性没有显着影响。需要进行前瞻性研究以进一步确定最有效的LDC方案。
■我们回顾性分析了在使用CD19定向CAR-T细胞产物axicabtageneciloleucel和tisagenlecleucel治疗之前接受LDC的单个机构的连续患者。在我们中心治疗的患者在2019年5月之前连续3天接受氟达拉滨30mg/m2和环磷酰胺500mg/m2。在该时间点之后,患者常规地接受氟达拉滨40mg/m2和环磷酰胺500mg/m2连续2天。从电子病历中获得每个队列的临床数据，并比较CART细胞功效和毒性的差异。
■从2018年6月至2023年8月，在接受CD19定向CART细胞治疗复发性非霍奇金淋巴瘤之前，对92名患者进行了LDC治疗。28名患者接受了为期3天的治疗方案，64例患者接受了2天的治疗方案。在总队列中，75％的患者接受了axicabtageneciloleucel，25％的患者接受了tisagenlecleucel。2天方案组和3天方案组的总反应率相似(69%vs75%,p=0.21)以及完全缓解率(50%对54%，p=0.82）。2-4级细胞因子释放综合征的2天和3天方案之间没有显着差异（55％vs50％，p=0.82)，2-4级免疫效应细胞相关神经毒性综合征(42%vs29%，p=0.25),或中性粒细胞减少症或血小板减少症的消退时间。3天治疗方案的血小板恢复时间超过60天的比率更高(9%vs27%,p=0.026)。
■随着有资格接受CAR-T细胞治疗的患者数量不断增加，优化治疗的每个组成部分是必要的。我们表明，使用氟达拉滨和环磷酰胺的LDC2天方案是可行的，对CART细胞功效或毒性没有显着影响。需要进行前瞻性研究以进一步确定最有效的LDC方案。
