Comparing CAR T-cell toxicity grading systems: application of the ASTCT grading system and implications for management
Comparing CAR T-cell toxicity grading systems: application of the ASTCT grading system and implications for management
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DOI：
10.1182/bloodadvances.2019000952
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发表时间：
2020-02-25
期刊：
影响因子：
7.5
通讯作者：
Perales, Miguel-Angel
中科院分区：
文献类型：
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作者：
Pennisi, Martina;Jain, Tania;Perales, Miguel-Angel
目前，各种分级系统用于嵌合抗原受体（CAR）T细胞相关毒性、细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）。我们比较了最近提出的美国移植和细胞治疗学会（ASTCT）分级系统与2个成人人群的其他分级评分：接受1928 z CAR T细胞治疗的B细胞急性淋巴细胞白血病（B-ALL）患者（n = 53）（clinicaltrials.gov#NCT01044069），以及在美国食品和药物管理局批准后用axicabtagene-ciloleucel（axi-cel）或tisagenlecleucel治疗的弥漫性大B细胞淋巴瘤（DLBCL）患者（n = 49）。根据ASTCT分级，82%的患者患有CRS，B-ALL组为87%，DLBCL组为77%（axi-cel：86%，tisagenlecleucel：54%），而50%的患者经历了ICANS，B-ALL组为55%，DLBCL组为45%（axi-cel：55%，tisagenlecleucel：15%）。所有分级系统分别在99%和91%的病例中同意CRS和ICANS诊断。然而，当按等级分析时，CRS和ICANS的每个系统中分别只有25%和54%的患者具有相同的等级，因为不同的系统对症状评分不同（升级或降级其严重程度），导致最终等级不一致。对DLBCL患者可能的管理影响的调查显示，目前指南中对托珠单抗和类固醇的不同建议可能导致过度治疗或延迟治疗。此外，由于这些准则是基于单一产品和不同的分级系统，它们不能普遍适用。为了避免不同产品在评估和管理毒性方面的差异，我们建议在临床试验和实践中使用统一的分级，并制定具有产品特定适应症的配对管理指南。
Various grading systems are currently used for chimeric antigen receptor (CAR) T-cell-related toxicity, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). We compared the recently proposed American Society for Transplantation and Cellular Therapy (ASTCT) grading system to other grading scores in 2 populations of adults: patients (n = 53) with B-cell acute lymphoblastic leukemia (B-ALL) treated with 1928z CAR T-cells (clinicaltrials.gov #NCT01044069), and patients (n = 49) with diffuse large B-cell lymphoma (DLBCL) treated with axicabtagene-ciloleucel (axi-cel) or tisagenlecleucel after US Food and Drug Administration approval. According to ASTCT grading, 82% of patients had CRS, 87% in the B-ALL and 77% in the DLBCL groups (axi-cel: 86%, tisagenlecleucel: 54%), whereas 50% of patients experienced ICANS, 55% in the B-ALL and 45% in the DLBCL groups (axi-cel: 55%, tisagenlecleucel: 15%). All grading systems agreed on CRS and ICANS diagnosis in 99% and 91% of cases, respectively. However, when analyzed grade by grade, only 25% and 54% of patients had the same grade in each system for CRS and ICANS, respectively, as different systems score symptoms differently (upgrading or downgrading their severity), leading to inconsistent final grades. Investigation of possible management implications in DLBCL patients showed that different recommendations on tocilizumab and steroids across current guidelines potentially result in either overtreating or delaying treatment. Moreover, because these guidelines are based on single products and different grading systems, they cannot be universally applied. To avoid discrepancies in assessing and managing toxicities of different products, we propose that unified grading be used across clinical trials and in practice and that paired management guidelines with product-specific indications be developed.