决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Impact of IL-6 and ferritin dynamics on clinical outcomes after anti-CD19 CAR-T cell therapy in diffuse large B-cell lymphoma patients.
连续检测IL-6和铁蛋白与CRS相关炎症状态有关。第+7天IL-6和第+7天铁蛋白显示出与死亡率的探索性关联。
白细胞介素-6(IL-6)和铁蛋白在CAR-T 细胞治疗期间常规监测;然而,其时间动态变化及与结局相关的意义仍未被充分阐明。本研究旨在评估接受抗CD19 CAR-T治疗的弥漫性大B细胞淋巴瘤(DLBCL)患者在多个时间点的IL-6和铁蛋白的价值。
共回顾性分析54例患者(中位年龄49.0岁;64.8%为男性)。输注后第1天、第7天、第14天检测IL-6和铁蛋白水平,峰值定义为输注后前14天内的最高水平。采用Cox比例风险回归评估生存,采用logistic回归分析二分类结局,并进行Firth惩罚回归作为敏感性分析。采用Spearman相关性分析描述IL-6、铁蛋白与常规实验室指标之间的关系。
68.5%的患者发生CRS,客观缓解率为70.4%。发生CRS的患者在第1天(P = 0.003)和峰值水平(P = 0.005)时IL-6水平显著更高。第7天的IL-6与死亡率相关(OR = 1.625,95% CI:1.076-2.737,P = 0.038)。铁蛋白在所有时间点均与CRS相关,并显示出与死亡率的探索性关联,但与治疗反应无关。第7天IL-6对死亡状态的AUC在数值上最高,而第14天铁蛋白对CRS的AUC在数值上最高。IL-6在第+1天、第+7天和峰值时与白蛋白呈负相关,而铁蛋白在第+1天、第+7天和峰值时与RBC计数呈负相关。
BACKGROUND: Interleukin-6 (IL-6) and ferritin are routinely monitored during chimeric antigen receptor T-cell (CAR-T) therapy; however, their temporal dynamics and outcome-specific relevance remain inadequately characterized. This study aimed to evaluate the value of IL-6 and ferritin at multiple time points in patients with diffuse large B-cell lymphoma (DLBCL) receiving anti-CD19 CAR-T therapy. METHODS: A total of 54 patients (median age 49.0 years; 64.8% male) were retrospectively analyzed. Post-infusion IL-6 and ferritin levels were measured on day 1, day 7, day 14, and the peak value was defined as the highest level within the first 14 days after infusion. Survival was evaluated using Cox proportional hazards regression, while logistic regression was used for binary outcomes, with Firth penalized regression performed as a sensitivity analysis. Spearman correlation was used to characterize relationships between IL-6, ferritin, and routine laboratory parameters. RESULTS: CRS occurred in 68.5% of patients, and the objective response rate was 70.4%. IL-6 levels were significantly higher in patients with CRS at day 1 ( P = 0.003) and at peak levels ( P = 0.005). IL-6 on day 7 was associated with mortality (OR = 1.625, 95% CI: 1.076-2.737, P = 0.038). Ferritin was associated with CRS at all time points and showed an exploratory association with mortality, but not with treatment response. Day 7 IL-6 showed the numerically highest AUC for death status, whereas Day 14 ferritin showed the numerically highest AUC for CRS. IL-6 was negatively correlated with albumin at Day +1, Day +7, and peak, whereas ferritin was negatively correlated with RBC count at Day +1, Day +7, and peak. CONCLUSION: Serial IL-6 and ferritin measurements were associated with CRS-related inflammatory status. Day +7 IL-6 and Day +7 ferritin showed exploratory associations with mortality.
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