Abstract：
BACKGROUND: The application of CD19-directed chimeric antigen receptor T (CAR T) cell therapy has improved outcomes for thousands of patients with non-Hodgkin B cell lymphoma (NHL). The toxicities associated with various CAR T cell products, however, can be severe and difficult to anticipate.
METHODS: In this systematic review and meta-analysis, we set out to determine whether there are measurable differences in common toxicities, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), cytopenias, and infections, between CAR T products that are commercially available for the treatment of NHL.
RESULTS: After a stringent study selection process, we used a cohort of 1364 patients enrolled in 15 prospective clinical trials investigating the use of axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel). We found that the rates of CRS and ICANS were significantly higher with axi-cel as compared to both liso-cel and tisa-cel. Conversely, we demonstrated that rates of all-grade and severe neutropenia were significantly greater with liso-cel. Febrile neutropenia and all-grade infection rates did not differ significantly between products though rates of severe infection were increased with axi-cel.
CONCLUSIONS: Overall, this study serves as the first to delineate toxicity profiles associated with various available CAR T products. By better understanding associated toxicities, it may become possible to tailor therapies towards individual patients and anticipate the development of toxicities at earlier stages.
METHODS: In this systematic review and meta-analysis, we set out to determine whether there are measurable differences in common toxicities, including cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), cytopenias, and infections, between CAR T products that are commercially available for the treatment of NHL.
RESULTS: After a stringent study selection process, we used a cohort of 1364 patients enrolled in 15 prospective clinical trials investigating the use of axicabtagene ciloleucel (axi-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel). We found that the rates of CRS and ICANS were significantly higher with axi-cel as compared to both liso-cel and tisa-cel. Conversely, we demonstrated that rates of all-grade and severe neutropenia were significantly greater with liso-cel. Febrile neutropenia and all-grade infection rates did not differ significantly between products though rates of severe infection were increased with axi-cel.
CONCLUSIONS: Overall, this study serves as the first to delineate toxicity profiles associated with various available CAR T products. By better understanding associated toxicities, it may become possible to tailor therapies towards individual patients and anticipate the development of toxicities at earlier stages.
摘要：
背景：针对CD19的嵌合抗原受体T（CART）细胞疗法的应用改善了成千上万的非霍奇金B细胞淋巴瘤（NHL）患者的预后。与各种CART细胞产品相关的毒性，然而,可能是严重的，很难预测。
方法：在本系统综述和荟萃分析中，我们着手确定常见毒性是否存在可测量的差异，包括细胞因子释放综合征（CRS），免疫效应细胞相关神经毒性综合征（ICANS），血细胞减少,和感染，在市售用于治疗NHL的CART产品之间。
结果：经过严格的研究选择过程，我们在15项前瞻性临床试验中纳入了1364名患者的队列，调查了axicabtageneciloleucel（axi-cel）的使用，lisocabtagenemaraleucel(liso-cel),和tisagenlecleucel(tisa-cel)。我们发现，与iso-cel和tisa-cel相比，axi-cel的CRS和ICANS的比率明显更高。相反，我们证明,使用肌细胞时,全级别和重度中性粒细胞减少的发生率显著增高.尽管严重感染率随axi-cel的增加而增加，但产品之间的嗜中性粒细胞减少症和所有等级的感染率没有显着差异。
结论：总体而言，这项研究首次描述了与各种现有CART产品相关的毒性特征.通过更好地了解相关的毒性，可能有可能针对个体患者定制治疗方法，并在早期阶段预测毒性的发展。
方法：在本系统综述和荟萃分析中，我们着手确定常见毒性是否存在可测量的差异，包括细胞因子释放综合征（CRS），免疫效应细胞相关神经毒性综合征（ICANS），血细胞减少,和感染，在市售用于治疗NHL的CART产品之间。
结果：经过严格的研究选择过程，我们在15项前瞻性临床试验中纳入了1364名患者的队列，调查了axicabtageneciloleucel（axi-cel）的使用，lisocabtagenemaraleucel(liso-cel),和tisagenlecleucel(tisa-cel)。我们发现，与iso-cel和tisa-cel相比，axi-cel的CRS和ICANS的比率明显更高。相反，我们证明,使用肌细胞时,全级别和重度中性粒细胞减少的发生率显著增高.尽管严重感染率随axi-cel的增加而增加，但产品之间的嗜中性粒细胞减少症和所有等级的感染率没有显着差异。
结论：总体而言，这项研究首次描述了与各种现有CART产品相关的毒性特征.通过更好地了解相关的毒性，可能有可能针对个体患者定制治疗方法，并在早期阶段预测毒性的发展。
