Baseline Tumor Burden Assessed With AI-Guided PET/CT Total Metabolic Tumor Volume (TMTV) and LDH Levels Predict Efficacy of CAR-T in Aggressive B-Cell Lymphoma

Disease burden is a critical determinant of outcomes in CAR-T therapy for B-cell lymphomas, and one of the most widely used techniques for its assessment is Total Metabolic Tumor Volume (TMTV) measured via [18F]FDG PET/CT. Biological parameters may further refine the risk profile. We analyzed baseline [18F]FDG PET/CT scans from 40 patients treated with CAR-T, using an AI-based automated segmentation algorithm to determine TMTV. Our analysis identified that a baseline TMTV greater than 48.4 cm³ and elevated LDH independently predicted progression-free survival (PFS) after CAR-T therapy (HR 4.28, p = 0.007, and HR 8.20, p < 0.001, respectively). We then proposed a 0-to-2 risk score, assigning one point each for elevated TMTV and elevated LDH. All patients with a score of two experienced a PFS of less than 90 days following CAR-T infusion. Among the remaining patients, those with 0 points versus 1 point demonstrated a 3-month PFS of 100% versus 85%, a 6-month PFS of 92% versus 53%, and a 12-month PFS of 83% versus 53%, respectively. Importantly, patients with high baseline TMTV who achieved a TMTV reduction to less than 1.99 cm³ by day 30 had a PFS of 66%, significantly better compared to those who did not achieve this reduction. AI-guided TMTV assessment, combined with LDH levels, provides a rapid and sensitive method for risk stratification at the bedside, which could help optimize patient management prior to CAR-T therapy.