Post-CAR T-Cell Therapy Failure Metabolic Parameters Predict Survival and Response in Large B-Cell Lymphoma

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.