Systematic review and meta−analysis of PET−based prognostic metrics in CAR−T treatment of DLBCL

Objectives This study aims to conduct a systematic review and meta-analysis to investigate how imaging parameters derived from 18 F-FDG positron emission tomography/computed tomography (PET/CT) predict treatment outcomes in patients with diffuse large B-cell lymphoma (DLBCL) receiving chimeric antigen receptor T-cell (CAR-T) therapy. Methods A comprehensive search was conducted in PubMed, Embase, Cochrane Library, and Web of Science databases to retrieve relevant literature from their inception to December 24, 2024. This study is registered in PROSPERO (CRD42025634694). The protocol was completed in accordance with the PRISMA guidelines recommended by the EJNMMI authors’ guide. Cohort studies were included that enrolled patients diagnosed with DLBCL via 18 F-FDG PET/CT and who received CAR-T therapy. Fixed-effect and random-effects models were applied using Stata software to calculate pooled hazard ratios (HR) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic. Results A total of 14 studies were included, involving 1,088 patients (aged 20 to 86 years) diagnosed with DLBCL based on 18 F-FDG PET/CT imaging findings. Univariate analysis demonstrated significant associations between several PET-derived parameters and survival outcomes: SUVmax was predictive of both overall survival (OS) (HR: 1.61; 95% CI: 1.20–2.18) and progression-free survival (PFS) (HR: 1.47; 95% CI: 1.09–1.98); higher MTV levels were associated with decreased OS (HR: 2.81; 95% CI: 1.23–6.45) and PFS (HR: 2.39; 95% CI: 1.24–4.61); and TMTV and TLG were also prognostic for PFS and OS. Notably, elevated LDH was linked to inferior OS (HR: 2.76; 95% CI: 2.06–3.71) and PFS (HR: 1.95; 95% CI: 1.50–2.54). ECOG performance status (HR: 2.14; 95% CI: 1.38–3.31) and DS (HR: 6.02; 95% CI: 2.80–12.94) were significantly associated with OS, while IPI was also predictive of OS (HR: 2.04; 95% CI: 1.19–3.50). Elevated LDH and impaired ECOG performance status were independently linked to poorer OS in multivariate analysis (HRs: 3.52 and 2.58, respectively), while the IPI score remained a standalone determinant of PFS (HR: 3.07; 95% CI: 1.59–5.93). Conclusion The outcomes of DLBCL cases managed using CAR-T cells can be effectively predicted using both metabolic metrics from 18 F-FDG PET/CT and conventional clinical prognostic markers. Systematic Review Registration https://www.crd.york.ac.uk/prospero , identifier CRD42025634694.