Baseline Metabolic Tumor Volume predicts outcome in patients with high tumor burden follicular lymphoma.

Objectives Identification of patients at high risk of progression and early death amongst those with high tumor burden follicular lymphoma (HTBFL) is unsatisfactory with current prognostic models. This study aimed to determine the prognostic impact of the total metabolic tumor volume (TMTV) measured on baseline FDG/PET-CT and its added value to these existing models.

Methods A pooled analysis of patient data and centrally reviewed baseline PET-CT scans for 181 patients with HTBFL receiving R-chemotherapy within three prospective trials was performed . TMTV was computed using the 41% SUVmax thresholding method and the optimal cut-off for survival prediction was determined with X-tile and Receiver Operating Curve analysis.

Results Median age was 55 years; 92% of patients had stage III/IV disease; 37% had FLIPI 3-5; 31% had FLIPI2 3-5. Median SUVmax was 10 (Q1-Q3:7-14) With a median follow-up of 64 months, 5y-PFS was 55% and 5y-OS 92%. Only two patients had disease transformation. Median TMTV was 297cm3 (Q1-Q3: 135-567). The optimal cut-off was 510cm3. The 29% of patients with TMTV >510cm3 had a markedly inferior survival. 5y-PFS was 33% vs. 65%, (HR=2.76, p<0.0001); 5y-OS was 85% vs. 95%, (HR=3.4, p=0.010).. On multivariate analysis TMTV (HR=2.1, p=0.003) and FLIPI2 (HR 2.0, p=0.002) were independent predictors of PFS. In combination they identify three risk groups: high TMTV and FLIPI2 3-5 with 5-y PFS 20% (p<0.0001, HR=4.8), high TMTV or FLIPI2 3-5 with 5-y PFS 46%, (p=0.006, HR=2.1), and low TMTV and FLIP2 0-2 with 5-y PFS 69%.

Conclusions Baseline TMTV is a strong independent predictor of outcome in HTBFL. In combination with FLIPI2 it identifies patients at high risk of early progression. It warrants further validation as a biomarker for development of frontline PET-adapted approaches in FL.