CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:EEG features and synek scale indicate severity of neurotoxicity in adult patients treated with CD19 CAR T-cell therapy.
EEG features and synek scale indicate severity of neurotoxicity in adult patients treated with CD19 CAR T-cell therapy.
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接受嵌合抗原受体(CAR)T细胞治疗后发生免疫效应细胞相关神经毒性综合征(ICANS)的患者,通常会接受脑电图(EEG)评估。
我们假设,EEG特征及用于衡量EEG异常程度的Synek评分与ICANS严重程度相关。本研究回顾性分析了纪念斯隆凯特琳癌症中心于2010至2019年接受CAR-T 治疗的125例成人患者,包括53例接受1928z CAR-T 细胞治疗的B急性淋巴细胞白血病(B-ALL)患者(NCT01044069),以及72例接受商业化CAR-T 产品阿基仑赛或替沙格列赛治疗的大B细胞淋巴瘤(LBCL)患者。研究收集视频EEG监测资料(B-ALL患者27例,LBCL患者20例),并记录47例符合条件患者每日的EEG特征、Synek评分和ICANS分级。Synek评分与ICANS分级呈正相关(相关系数0.47,95% CI:0.31–0.60)。单变量模型进一步证实,较高Synek评分(3或4)与较高ICANS分级相关(OR=15.2;95% CI:7.8–29.7,p<0.0001)。在单变量模型中,EEG背景不连续、后部优势节律缺失及出现全身性尖波等特征均与较高ICANS分级显著相关。在多变量模型中,背景不连续(OR=4.2,95% CI:1.3–13.8,p=0.02)及后部优势节律缺失(OR=10.5,95% CI:4.6–23.9,p<0.0001)与较高ICANS分级显著相关。
总体而言,EEG背景不连续及后部优势节律缺失均独立关联于更严重的神经毒性。此外,数据提示Synek评分可能是神经毒性严重程度的标志。
Patients who develop chimeric antigen receptor (CAR) T-cell-related immune effector cell-associated neurotoxicity syndrome (ICANS) frequently undergo evaluation with electroencephalography (EEG).
We hypothesize that EEG features and Synek scale score, a measure of degree of EEG abnormality, are associated with ICANS severity.
Here, we performed a retrospective review of 125 adult patients at Memorial Sloan Kettering Cancer Center (MSKCC) who received CAR-T cell therapy from 2010 to 2019, including 53 patients with B-acute lymphoblastic leukemia treated with 1928z CAR T cells (NCT01044069) and 72 patients with large B-cell lymphoma (LBCL) treated with the commercial CAR T products axicabtagene ciloleucel or tisagenlecleucel.
We collected video EEG monitoring (27 with B-ALL and 20 with LBCL) and recorded daily EEG features, Synek scores, and ICANS grade for 47 eligible patients. Synek scale and ICANS grade were positively correlated (correlation coefficient 0. 47, 95% CI: 0. 31-0. 60). This was further corroborated in the univariable model associating high Synek scale (3 or 4) with high ICANS grade (OR = 15. 2; 95%CI:7. 8-29. 7, p < 0. 0001).
EEG features such as discontinuity, absence of posterior dominant rhythm, and presence of generalized sharp waves were statistically significantly associated with higher ICANS grade in univariable models. In the multivariable model, discontinuity (OR = 4. 2 (95%CI:1. 3-13. 8, p = 0. 02) and absence of posterior dominant rhythm (OR = 10. 5 (95%CI:4. 6-23. 9, p < 0. 0001) were statistically associated with higher ICANS grade.
Overall, EEG discontinuity and absence of posterior dominant rhythm were independently associated with higher severity of neurotoxicity.
Further, our data suggest that Synek Scale, may be a severity marker for neurotoxicity.
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