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:Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma.
Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma.
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自体抗CD19嵌合抗原受体(CAR)T细胞目前已在复发/难治性(R/R)大B细胞淋巴瘤(LBCL)的常规实践中使用。严重(3级)细胞因子释放综合征(CRS)和免疫效应细胞相关神经毒性(ICANS)仍然是最令人担忧的急性毒性反应,导致频繁入住重症监护室(ICU)、延长住院时间,并显著增加治疗费用。
我们基于通过DESCAR-T 登记处采集的患者数据,报告了法国925例接受axicabtagene ciloleucel(axi-cel)或tisagenlecleucel(tisa-cel)治疗的LBCL患者大型队列中CRS和ICANS的发生率及结局。任何级别的CRS发生于778例患者(84.1%),其中74例患者(8.0%)为3级或以上CRS;任何级别的ICANS发生于375例患者(40.5%),其中112例患者(12.1%)为3级ICANS。基于多变量分析筛选出的参数,衍生出两个独立的预后评分系统(PSS),一个用于3级CRS,一个用于3级ICANS。CRS-PSS包括大包块疾病、血小板计数 < 150 G/L、C反应蛋白(CRP)水平 > 30 mg/L以及未接受桥接治疗或桥接治疗后疾病稳定或进展(SD/PD)。CRS-PSS评分 > 2的患者发生3级CRS的风险显著更高。ICANS-PSS包括女性、低血小板水平(< 150 G/L)、使用axi-cel以及未接受桥接治疗或桥接治疗后SD/PD。CRS-PSS评分 > 2的患者发生3级ICANS的风险显著更高。两个评分均在接受tisa-cel或axi-cel治疗的国际患者队列中进行了外部验证。
Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment.
We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84. 1%), with 74 patients (8. 0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40. 5%), with 112 patients (12. 1%) with grade 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade 3 CRS and one for grade 3 ICANS.
CRS-PSS included bulky disease, a platelet count < 150 G/L, a C-reactive protein (CRP) level > 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade 3 CRS.
ICANS-PSS included female sex, low level of platelets (< 150 G/L), use of axi-cel and no bridging therapy or SD/PD after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.
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