Background: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of relapsed/refractory large B-cell lymphoma (LBCL), but its administration is often complicated by cytokine release syndrome (CRS). Interleukin-6 (IL-6) is widely used to monitor CRS, though its clinical value diminishes after tocilizumab administration. We aimed to evaluate serum amyloid A (SAA), a dynamic acute-phase reactant, as a treatment-independent biomarker of inflammation and toxicity in CAR-T recipients.Methods: This retrospective study included 43 adults with LBCL treated with axicabtagene ciloleucel. SAA and other inflammatory markers were assessed from lymphodepletion through day +11 post-infusion. CRS and ICANS were graded per ASTCT criteria. Statistical analyses included Mann–Whitney U tests, Spearman’s correlation, and ROC curve analysis to evaluate predictive performance.Results: SAA levels peaked at day +4 and normalized by day +11, displaying wave-like kinetics. Levels were significantly higher in patients with any-grade CRS at early timepoints but showed no association with ICANS. SAA correlated strongly with CRP, suPAR, sST2, fibrinogen, ferritin, procalcitonin, and IL-6. Compared to IL-6, SAA was more predictive of CRS at day +2 and +4, and unaffected by tocilizumab. Baseline SAA also correlated with the mEASIX score, suggesting linkage to endothelial stress. Non-responders at 3-month PET had higher baseline SAA than responders (196.0 vs. 17.7 mg/L,p= 0.036), with ROC analysis yielding an AUC of 0.74 and an optimal threshold of 79.8 mg/L.Conclusions: SAA is a robust and dynamic marker of systemic inflammation, with potential utility in both toxicity monitoring and response prediction in the CAR-T setting. Its independence from IL-6 modulation positions it as a promising biomarker for future integration into clinical algorithms.
背景：嵌合抗原受体（CAR）T细胞疗法已彻底改变了复发/难治性大B细胞淋巴瘤（LBCL）的治疗，但其应用常因细胞因子释放综合征（CRS）而复杂化。白细胞介素-6（IL-6）被广泛用于监测CRS，但在托珠单抗给药后其临床价值降低。本研究旨在评估血清淀粉样蛋白A（SAA）——一种动态急性期反应物——作为CAR-T治疗患者中与治疗无关的炎症及毒性生物标志物的价值。 方法：这项回顾性研究纳入了43例接受阿基仑赛治疗的LBCL成年患者。从淋巴细胞清除期至输注后第+11天，对SAA及其他炎症标志物进行了评估。CRS和免疫效应细胞相关神经毒性综合征（ICANS）依据ASTCT标准分级。统计分析包括曼-惠特尼U检验、斯皮尔曼相关性分析及ROC曲线分析，以评估预测性能。 结果：SAA水平在第+4天达到峰值，至第+11天恢复正常，呈现波浪式动力学特征。在早期时间点，发生任何级别CRS的患者SAA水平显著更高，但与ICANS无关联。SAA与C反应蛋白（CRP）、可溶性尿激酶型纤溶酶原激活物受体（suPAR）、可溶性生长刺激表达基因2蛋白（sST2）、纤维蛋白原、铁蛋白、降钙素原及IL-6均呈强相关。与IL-6相比，SAA在第+2天和第+4天对CRS的预测能力更强，且不受托珠单抗影响。基线SAA水平还与改良内皮激活及应激指数（mEASIX）评分相关，提示其与内皮应激存在关联。3个月PET评估无应答者的基线SAA水平高于应答者（196.0 vs. 17.7 mg/L，p=0.036），ROC分析显示曲线下面积（AUC）为0.74，最佳阈值为79.8 mg/L。 结论：SAA是一种稳健且动态的全身性炎症标志物，在CAR-T治疗背景下，具有用于毒性监测和疗效预测的潜在价值。其不受IL-6调节影响的特点，使其成为未来整合入临床诊疗流程中极具前景的生物标志物。
Tracking Inflammation in CAR-T Therapy: The Emerging Role of Serum Amyloid A (SAA)
肿瘤(癌症)患者之家