Metabolic tumor volume predicts outcome in advanced stage follicular lymphoma patients from the Relevance trial.

We investigated the prognostic value of baseline PET parameters for patients with treatment-naïve follicular lymphoma (FL) in the phase 3 RELEVANCE trial, comparing the immunomodulatory combination of lenalidomide and rituximab (R2) vs R-chemotherapy (R-chemo), with both regimens followed by R maintenance therapy.Baseline characteristics of the entire PET-evaluable population (n=406/1032) were well balanced between treatment arms. SUVmax and SDmax, the standardized distance between two lesions the furthest apart were extracted. Total metabolic tumor volume (TMTV) was computed using the 41%SUVmax method.With a median follow-up of 6.5 years, the 6y-PFS was 57.8%, the median TMTV was 284 cm3, SUVmax 11.3 and SDmax 0.32 m-1, with no significant difference between arms. High TMTV (> 510 cm3) and FLIPI were associated with an inferior PFS (p=0.013 and p=0.006), whereas SUVmax and SDmax were not (p=0.08 and p=0.12). In multivariable analysis, FLIPI and TMTV remained significantly associated with PFS (p=0.0119 and p=0.0379). These two adverse factors combined stratified the overall population into 3 risk groups: patients with no risk factors (40%), with one factor (44%), or with both (16%), with a 6y-PFS of 67.7%, 54.5% and 41.0% respectively. No significant interaction between treatment arms and TMTV or FLIPI (p=0.31 and p=0.59) were observed. The high-risk group (high TMTV and FLIPI 3-5) had a similar PFS in both arms (p=0.45) with a median PFS of 68.4% in the R chemo arm vs 71.4 % in the R2 arm.Baseline TMTV is predictive of PFS, independently of FLIPI, in patients with advanced FL even in the context of antibody maintenance.