文章：

基于人群的外部验证：EASIX评分预测CAR T细胞相关毒性的有效性评估

Population-Based External Validation of the EASIX Scores to Predict CAR T-Cell-Related Toxicities

原文发布日期：16 November 2023

DOI: 10.3390/cancers15225443

类型: Article

开放获取: 是

英文摘要：

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can hamper the clinical benefit of CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (r/r LBCL). To assess the risk of CRS and ICANS, the endothelial activation and stress index (EASIX), the modified EASIX (m-EASIX), simplified EASIX (s-EASIX), and EASIX with CRP/ferritin (EASIX-F(C)) were proposed. This study validates these scores in a consecutive population-based cohort. Patients with r/r LBCL treated with axicabtagene ciloleucel were included (n= 154). EASIX scores were calculated at baseline, before lymphodepletion (pre-LD) and at CAR T-cell infusion. The EASIX and the s-EASIX at pre-LD were significantly associated with ICANS grade ≥ 2 (bothp= 0.04), and the EASIX approached statistical significance at infusion (p= 0.05). However, the predictive performance was moderate, with area under the curves of 0.61–0.62. Validation of the EASIX-FC revealed that patients in the intermediate risk group had an increased risk of ICANS grade ≥ 2 compared to low-risk patients. No significant associations between EASIX scores and CRS/ICANS grade ≥ 3 were found. The (m-/s-) EASIX can be used to assess the risk of ICANS grade ≥ 2 in patients treated with CAR T-cell therapy. However, due to the moderate performance of the scores, further optimization needs to be performed before broad implementation as a clinical tool, directing early intervention and guiding outpatient CAR T-cell treatment.

摘要翻译： 

细胞因子释放综合征（CRS）与免疫效应细胞相关神经毒性综合征（ICANS）可能影响嵌合抗原受体T细胞疗法在复发/难治性大B细胞淋巴瘤患者中的临床获益。为评估CRS与ICANS风险，研究提出了内皮细胞活化应激指数（EASIX）、改良EASIX（m-EASIX）、简化EASIX（s-EASIX）及联合C反应蛋白/铁蛋白的EASIX（EASIX-F(C)）。本研究在基于人群的连续队列中对这些评分体系进行验证。纳入接受阿基仑赛治疗的复发/难治性大B细胞淋巴瘤患者（n=154），分别计算基线期、淋巴细胞清除前及CAR T细胞输注时的EASIX评分。淋巴细胞清除前的EASIX与s-EASIX评分与≥2级ICANS显著相关（p值均为0.04），输注时EASIX评分亦接近统计学显著性（p=0.05）。但预测效能中等，曲线下面积范围为0.61-0.62。EASIX-FC验证显示中危组患者较低危组发生≥2级ICANS的风险更高。未发现EASIX评分与≥3级CRS/ICANS存在显著关联。（m-/s-）EASIX可用于评估CAR T细胞治疗患者发生≥2级ICANS的风险，但由于评分体系预测效能有限，在作为指导早期干预和门诊CAR T细胞治疗的临床工具广泛推广前，仍需进一步优化。

原文链接：

Population-Based External Validation of the EASIX Scores to Predict CAR T-Cell-Related Toxicities