Plasma metabolomics analysis was performed on 44 patients with relapsed/refractory B-cell non-Hodgkin lymphoma (r/r/B-NHL) infused with approved CD19.CAR-T cell products at the time of pre-lymphodepletion (PLD) and at day +1, +7, and +30 after CAR-T cell infusion. At the PLD time point, a metabolic profile characterized by high lipoproteins and lactate and low glucose contributed to poor outcome prediction in association with high lactate dehydrogenase levels. At day+1, higher plasma levels of lipid metabolism products and lower glucose and glycoproteins levels were observed in tisa-cel compared to axi-cel-treated patients. At day+30, discriminant analysis found two clusters in a subgroup of patients, one with CR lasting one year after therapy, and another who relapsed within one year (relapsed>D30). This latter showed a higher content of N-GlycA, a known biomarker of systemic inflammation that is also correlated with C-reactive protein in our case setting of relapsing patients. Our data show complex metabolomic changes that track the evolution of the disease and drug activity in the first 30 days of CAR-T cell therapy. Conceivably, a pro-inflammatory drift may be linked to a forthcoming disease relapse in CAR-T patients.

中文翻译：

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接受 CD19 嵌合抗原受体 T 细胞治疗的复发/难治性 B 细胞非霍奇金淋巴瘤患者的代谢特征演变及其对临床结果的影响。


对 44 例输注已批准的 CD19 的复发/难治性 B 细胞非霍奇金淋巴瘤 （r/r/B-NHL） 患者进行了血浆代谢组学分析。淋巴细胞清除前 （PLD） 时以及 CAR-T 细胞输注后第 +1、+7 和 +30 天的 CAR-T 细胞产物。在 PLD 时间点，以高脂蛋白和乳酸以及低葡萄糖为特征的代谢谱导致与高乳酸脱氢酶水平相关的不良结果预测。在第 +1 天，与 axi-cel 治疗的患者相比，tisa-cel 观察到血浆脂质代谢产物水平较高，葡萄糖和糖蛋白水平较低。在第 +30 天，判别分析在一个患者亚组中发现了两个集群，一个在治疗后 CR 持续一年，另一个在一年内复发 （复发>D30）。后者显示 N-GlycA 含量较高，N-GlycA 是已知的全身炎症生物标志物，在我们的复发患者病例中也与 C 反应蛋白相关。我们的数据显示了复杂的代谢组学变化，这些变化跟踪了 CAR-T 细胞疗法前 30 天内疾病的演变和药物活性。可以想象，促炎漂移可能与 CAR-T 患者即将发生的疾病复发有关。