Relapse and toxicity limit the effectiveness of chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL), yet biomarkers that predict outcomes and toxicity are lacking. We examined radiomic features extracted from pre-CAR-T 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) scans (n = 341) of 180 patients (121 male; median age, 66 years). Three conventional (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and 116 novel radiomic features were assessed, along with inflammatory markers, toxicities, and outcomes. At both pre-apheresis and pre-infusion time points, conventional PET features of disease correlated with elevated inflammatory markers. At pre-infusion, MTV was associated with grade ≥ 2 cytokine release syndrome (odds ratio [OR] for 100 mL increase: 1.08 [95% confidence interval (CI), 1.01–1.20], P = 0.031), and SUVmax was associated with failure to achieve complete response (CR) (OR 1.72 [95% CI, 1.24–2.43], P < 0.001). Higher pre-apheresis and pre-infusion MTV values were associated with shorter progression-free survival (PFS) (HR for 10-unit increase: 1.11 [95% CI, 1.05–1.17], P < 0.001; 1.04 [95% CI, 1.02–1.07], P < 0.001) and shorter overall survival (HR for 100-unit increase: 1.14 [95% CI, 1.07–1.21], P < 0.001; 1.04 [95% CI, 1.02–1.06], P < 0.001). A combined MTV and LDH measure stratified patients into high and low PFS risk groups. Multiple pre-infusion novel radiomic features were associated with CR. These quantitative conventional [18F]FDG PET/CT features obtained before CAR-T cell infusion, which were correlated with inflammation markers, may provide prognostic biomarkers for CAR-T therapy efficacy and toxicity. The use of conventional and novel radiomic features may thus help identify high-risk patients for earlier interventions.

中文翻译：

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传统和新型 [18F]FDG PET/CT 特征作为大 B 细胞淋巴瘤 CAR-T 细胞治疗结果的预测因子

复发和毒性限制了嵌合抗原受体 T 细胞 (CAR-T) 治疗大 B 细胞淋巴瘤 (LBCL) 的有效性，但缺乏预测结果和毒性的生物标志物。我们检查了从 180 名患者（121 名男性；中位年龄 66 岁）的 CAR-T 前 18F-氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描 ([18F]FDG PET/CT) 扫描 (n = 341) 中提取的放射组学特征。评估了三个常规特征（最大标准化摄取值 [SUVmax]、代谢肿瘤体积 [MTV]、总病变糖酵解 [TLG]）和 116 个新的放射组学特征，以及炎症标志物、毒性和结果。在血浆分离术前和输注前时间点，疾病的常规 PET 特征与炎症标志物升高相关。输注前，MTV 与 ≥ 2 级细胞因子释放综合征相关（增加 100 mL 的比值比 [OR]：1.08 [95% 置信区间 (CI)，1.01–1.20]，P = 0.031），并且 SUVmax 相关未能达到完全缓解 (CR)（OR 1.72 [95% CI, 1.24–2.43]，P < 0.001）。较高的血浆分离术前和输注前 MTV 值与较短的无进展生存期 (PFS) 相关（增加 10 个单位的 HR：1.11 [95% CI，1.05–1.17]，P < 0.001；1.04 [95% CI， 1.02–1.07]，P < 0.001）和较短的总生存期（增加 100 个单位的 HR：1.14 [95% CI，1.07–1.21]，P < 0.001；1.04 [95% CI，1.02–1.06]，P < 0.001 ）。 MTV 和 LDH 组合测量将患者分为高 PFS 风险组和低 PFS 风险组。多个输注前新的放射组学特征与 CR 相关。这些在 CAR-T 细胞输注前获得的定量常规 [18F]FDG PET/CT 特征与炎症标志物相关，可能为 CAR-T 治疗功效和毒性提供预后生物标志物。因此，使用传统和新颖的放射组学特征可能有助于识别高危患者以进行早期干预。