Standardized FDG-PET interpretation during CAR T-cell therapy in R/R DLBCL: a DESCAR-T study

CAR T-cell therapy has changed the management of relapsed/refractory (R/R) Diffuse large B-cell lymphoma (DLBCL). Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (PET/CT) plays a central role in lymphoma response assessment, but its prognostic use remains insufficiently standardized in this setting.

Patients from the French DESCAR-T registry treated in third line or beyond with commercial anti-CD19 CAR T-cells in real-life, and having centrally reviewed PET/CT before infusion, and at one month (M1) or three months (M3) post-infusion were included. For each visit, Total Metabolic Tumor Volume (TMTV) and SUVmax were measured. Deauville score (DS) and response according to 2014 Lugano classification were registered on follow-up PET/CT. Optimal TMTV cut-offs at baseline, M1 and M3 follow-up for progression-free survival (PFS) and overall survival (OS) and the prognostic impact of DS at M1 and M3 were determined.

A total of 212 R/R DLBCL patients were analysed. Baseline median SUVmax was 16.4 and median TMTV 41.3 cm3. A baseline TMTV cut-off of 30 cm³ significantly stratified patients for PFS and OS, in both univariate and multivariate analysis, along with LDH. Complete metabolic response (DS 1-3) at M1 was significantly associated with better PFS _M1 and OS _M1 than DS4-5 (for PFS _M1: median of 21.8 vs 1.8 vs months; p < 0.0001; for OS _M1: median not reached versus median of 6.3 months; p < 0.0001). DS5 identified patients with the worst outcomes (for PFS _M1: median of 0.1 month and for OS _M1: median of 4.5 months). Similarly, at M3 DS1-3 was associated with a better outcome than DS4-5, and patients with DS5 had the worst outcome. In patients without complete metabolic response residual TMTV provided additional prognostic value.

Baseline TMTV and metabolic response assessed by DS, together with residual TMTV on follow-up PET/CT, are strong prognostic biomarkers in R/R DLBCL patients treated with anti-CD19 CAR T-cells.