Department of Nuclear Medicine, Amiens-Picardie University Hospital, Amiens, France.
Department of Nuclear Medicine, University Rennes, CLCC Eugène Marquis, INSERM, LTSI-UMR 1099, Rennes, France.
Eur J Nucl Med Mol Imaging. 2024 Jan;51(2):481-489. doi: 10.1007/s00259-023-06427-6. Epub 2023 Sep 18.
Chimeric antigen receptor (CAR) T cells have established themselves as an effective treatment for refractory or relapsed large B cell lymphoma (LBCL). Recently, the sDmax, which corresponds to the distance separating the two farthest lesions standardized by the patient's body surface area, has appeared as a prognostic factor in LBCL. This study aimed to identify [F]FDG-PET biomarkers associated with prognosis and predictive of adverse events in patients treated with CAR T cells.
Patients were retrospectively included from two different university hospitals. They were being treated with CAR T cells for LBCL and underwent [F]FDG-PET just before CAR T cell infusion. Lesions were segmented semi-automatically with a threshold of 41% of the maximal uptake. In addition to clinico-biological features, sDmax, total metabolic tumor volume (TMTV), SUVmax, and uptake intensity of healthy lymphoid organs and liver were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. The occurrence of adverse events, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), was reported.
Fifty-six patients were included. The median follow-up was 9.7 months. Multivariate analysis showed that TMTV (cut-off of 36 mL) was an independent prognostic factor for PFS (p < 0.001) and that sDmax (cut-off of 0.15 m) was an independent prognostic factor for OS (p = 0.008). Concerning the occurrence of adverse events, a C-reactive protein level > 35 mg/L (p = 0.006) and a liver SUVmean > 2.5 (p = 0.027) before CAR T cells were associated with grade 2 to 4 CRS and a spleen SUVmean > 1.9 with grade 2 to 4 ICANS.
TMTV and sDmax had independent prognostic values, respectively, on PFS and OS. Regarding adverse events, the mean liver and spleen uptakes were associated with the occurrence of grade 2 to 4 CRS and ICANS, respectively. Integrating these biomarkers into the clinical workflow could be useful for early adaptation of patients management.
嵌合抗原受体（CAR）T 细胞已被确立为治疗难治性或复发性大 B 细胞淋巴瘤（LBCL）的有效方法。最近，sDmax（表示患者全身表面积标准化的两个最远病变之间的距离）作为 LBCL 的预后因素出现。本研究旨在确定与预后相关并可预测接受 CAR-T 细胞治疗的患者不良事件的[F]FDG-PET 生物标志物。
回顾性纳入来自两家不同大学医院的患者。他们因 LBCL 接受 CAR-T 细胞治疗，并在 CAR-T 细胞输注前进行[F]FDG-PET。使用 41%最大摄取阈值半自动分割病变。除临床生物学特征外，还收集 sDmax、总代谢肿瘤体积（TMTV）、SUVmax、健康淋巴器官和肝脏摄取强度。使用 Kaplan-Meier 方法估计无进展生存期（PFS）和总生存期（OS）。报告细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）等不良事件的发生情况。
共纳入 56 例患者。中位随访时间为 9.7 个月。多变量分析显示，TMTV（截断值为 36 mL）是 PFS 的独立预后因素（p < 0.001），sDmax（截断值为 0.15 m）是 OS 的独立预后因素（p = 0.008）。关于不良事件的发生，CAR-T 细胞前 C-反应蛋白水平>35 mg/L（p = 0.006）和肝脏 SUVmean >2.5（p = 0.027）与 2 至 4 级 CRS 相关，脾脏 SUVmean >1.9 与 2 至 4 级 ICANS 相关。
TMTV 和 sDmax 分别对 PFS 和 OS 具有独立的预后价值。关于不良事件，肝脏和脾脏摄取的平均值与 2 至 4 级 CRS 和 ICANS 的发生分别相关。将这些生物标志物纳入临床工作流程可能有助于早期调整患者管理。
