Baseline metabolic tumor volume predicts outcome in high-tumor-burden follicular lymphoma: A pooled analysis of three multicenter studies

Purpose: Identifying patients at high risk of progression and early death among those with high-tumor-burden follicular lymphoma (FL) is unsatisfactory with current prognostic models. This study aimed to determine the prognostic impact of the total metabolic tumor volume (TMTV) measured at baseline with [¹⁸F]fluorodeoxyglucose/positron emission tomography-computed tomography ([¹⁸F]FDG/PET-CT) scans and its added value to these models. Patients and Methods: A pooled analysis was performed by using patient data and centrally reviewed baseline PET-CT scans for 185 patients with FL who were receiving immunochemotherapy within three prospective trials. TMTV was computed by using the 41% maximum standardized uptake value thresholding method, and the optimal cutoff for survival prediction was determined. Results: Median age was 55 years, 92% of patients had stage III to IV disease, 37% had a Follicular Lymphoma International Prognostic Index (FLIPI) score of 3 to 5, and 31% had a FLIPI2 score of 3 to 5. With a median follow-up of 64 months, overall 5-year progression-free survival (PFS) was 55% and overall survival (OS) was 92%. Median TMTV was 297 cm³ (quartile 1 through quartile 3, 135 to 567 cm³). The optimal cutoff identified was 510 cm³, with a markedly inferior survival in the 29% of patients with TMTV > 510 cm³. Fiveyear PFS was 33% versus 65% (hazard ratio [HR], 2.90; P<.001), and 5-year OS was 85% versus 95% (HR, 3.45; P =.010). On multivariable analysis, TMTV (HR, 2.3; P =.002) and FLIPI2 score (HR, 2.2; P =.002) were independent predictors of PFS. In combination, they identify three risk groups: high TMTV and intermediateto-high FLIPI2 score with 5-year PFS of 20% (HR, 5.0; P <.001), high TMTV or intermediate-to-high FLIPI2 score with 5-year PFS of 46% (HR, 2.1; P =.007), and low TMTV and low FLIP2 with 5-year PFS of 69%. Conclusion: Baseline TMTV is a strong independent predictor of outcome in FL. In combination with FLIPI2 score, it identifies patients at high risk of early progression. It warrants further validation as a biomarker for development of first-line PET-adapted approaches in FL.