Total Metabolic Tumor Volume Is a Strong Independent Prognostic Factor in Follicular Lymphomas: Results From a Sub-Study of the FOLL12 Trial

Discordant results have been generated regarding the prognostic role of Total Metabolic Tumor Volume (TMTV) in Follicular Lymphoma (FL). The use of prospective data and the adoption of the newly defined standardized SUV4 method for calculating TMTV may generate stronger evidence. We conducted a pre-planned post hoc analysis of the prospective multicenter randomized phase III FOLL12 trial for newly diagnosed high tumor burden FL (grade 1-3a), which mandated baseline staging with PET. Baseline PET/CT scans were reviewed centrally, and TMTV was calculated using the fixed threshold of SUV4. Kaplan-Meier and Cox regression were used for survival analysis. The primary study endpoint was Progression free Survival (PFS). A total of 689 FL patients were available for TMTV definition. Median TMTV was 161 mL (IQR 50 to 388 mL) and the best cutoff value was set at 180 mL. Patients with high TMTV had a significantly lower 5-year PFS compared to those with low TMTV: 59% (95% CI, 53-65%) vs. 74% (95% CI, 69-78%) HR 1.61 (95% CI, 1.24-2.09). Prognostic role of TMTV was independent of study arm, chemotherapy regimen, and FLIPI2. Combined with FLIPI-2, we identified three groups with different 5-yr PFS rates, with the lowest rates (51%) for patients with high TMTV and high FLIPI2. Combined TMTV and FLIPI model was also prognostic to predict the risk of early progression and of death. Applying the SUV4 standard method pre-treatment TMTV is confirmed as a strong and independent predictor of PFS in FL patients. Integrating TMTV with FLIPI-2 improves risk assessment.