CAR-T 细胞治疗失败后的代谢参数预测大 B 细胞淋巴瘤的生存与缓解

18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) parameters have shown a significant prognostic role in relapsed/refractory large B-cell lymphoma (LBCL) patients undergoing CD19-targeted chimeric antigen receptor (CAR) T-cell therapy. While a substantial body of evidence exists on the prognostic value of PET/CT parameters in peri-CAR T setting, data available on the prognostic value of PET/CT parameters following CAR T-cell therapy failure is lacking.

Therefore, we sought to analyze the PET/CT scans of LBCL patients who experienced post-CAR T relapsed/progressive disease and subsequently received salvage therapies. Thirty-three LBCL patients who had PET-CT scans done demonstrating post-CAR T failure and then received salvage therapies [as a first salvage modality: RT alone, nine patients; combined modality therapy (CMT), seven patients; systemic therapy (ST) alone, 17 patients] were analyzed. The median follow-up after CAR T-cell infusion was 11. 7 months [interquartile range (IQR): 5. 1-24. 4 months], and the median follow-up after post-CAR T salvage therapy was 7. 3 months (IQR: 2. 7-19. 1 months). The median timeframe for the PET scan showing post-CAR T failure was 2. 4 months (IQR: 0. 96-5. 0 months).

On univariable analysis from salvage therapy start date, high metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were associated with inferior overall survival (OS) (Hazard ratio -HR = 8. 4, p < 0. 0001; HR = 3. 2, p = 0. 01, respectively). High MTV was associated with a non-significant trend of inferior progression-free survival (PFS) (HR = 3. 5, p = 0. 09).

High maximum standardized uptake value (SUVmax) was not associated with inferior OS or inferior PFS. On multivariable analysis from salvage therapy start date, high MTV (HR = 4. 6, 95% CI: 1. 5-14. 3, p = 0. 009) was identified to be an independent prognostic factor for inferior OS. High International Prognostic Index (IPI) ( 3) at the time of salvage therapy (HR = 2. 5, 95% CI: 1. 1-5. 6, p = 0. 02) was significantly associated with inferior PFS.

Our study shows that semiquantitative PET/CT metrics, especially MTV, are significant prognostic indicators of overall survival in this highly refractory population after CAR T-cell therapy failure, potentially refining prognostic and treatment approaches beyond conventional parameters like IPI.