Abstract：
CAR-T cells are widely recognized for their potential to successfully treat hematologic cancers and provide durable response. However, severe adverse events such as cytokine release syndrome (CRS) and neurotoxicity are concerning. Our goal is to assess CAR-T cell clinical trial publications to address the question of whether administration of CAR-T cells as dose fractions reduces toxicity without adversely affecting efficacy. Systematic literature review of studies published between January 2010 and May 2022 was performed on PubMed and Embase to search clinical studies that evaluated CAR-T cells for hematologic cancers. Studies published in English were considered. Studies in children (age < 18), solid tumors, bispecific CAR-T cells, and CAR-T cell cocktails were excluded. Data was extracted from the studies that met inclusion and exclusion criteria. Review identified a total of 18 studies that used dose fractionation. Six studies used 2-day dosing schemes and 12 studies used 3-day schemes to administer CAR-T cells. Three studies had both single dose and fractionated dose cohorts. Lower incidence of Grade ≥ 3 CRS and neurotoxicity was seen in fractionated dose cohorts in 2 studies, whereas 1 study reported no difference between single and fractionated dose cohorts. Dose fractionation was mainly recommended for high tumor burden patients. Efficacy of CAR-T cells in fractionated dose was comparable to single dose regimen within the same or historical trial of the same agent in all the studies. The findings suggest that administering dose fractions of CAR-T cells over 2-3 days instead of single dose infusion may mitigate the toxicity of CAR-T cell therapy including CRS and neurotoxicity, especially in patients with high tumor burden. However, controlled studies are likely needed to confirm the benefits of dose fractionation.
摘要：
CAR-T细胞因其成功治疗血液癌症并提供持久反应的潜力而被广泛认可。然而,细胞因子释放综合征(CRS)和神经毒性等严重不良事件令人担忧.我们的目标是评估CAR-T细胞临床试验出版物，以解决CAR-T细胞作为剂量分数的施用是否会降低毒性而不会对功效产生不利影响的问题。在PubMed和Embase上进行了2010年1月至2022年5月之间发表的研究的系统文献综述，以搜索评估血液癌症的CAR-T细胞的临床研究。考虑了以英语发表的研究。儿童研究（年龄<18岁），实体瘤,双特异性CAR-T细胞，排除CAR-T细胞混合物。数据来自符合纳入和排除标准的研究。综述确定了总共18项使用剂量分级的研究。6项研究使用2天的给药方案，12项研究使用3天的给药方案来施用CAR-T细胞。三项研究具有单剂量和分剂量组。在2项研究中，分级剂量队列中观察到≥3级CRS和神经毒性的发生率较低，而1项研究报告单剂量和分级剂量队列之间没有差异。主要推荐高肿瘤负荷患者的剂量分级。在所有研究中,在相同试剂的相同或历史试验中,分级剂量的CAR-T细胞的功效与单剂量方案相当。研究结果表明，在2-3天内给予CAR-T细胞的剂量分数而不是单剂量输注可以减轻CAR-T细胞疗法的毒性，包括CRS和神经毒性。尤其是肿瘤负荷高的患者。然而,可能需要对照研究来确认剂量分割的益处.
