Prognostic role of interim PET in patients with follicular lymphoma: a post-hoc study of FOLL12 trial by FIL

• Achievement of CMR after four cycles of first line immunochemotherapy is associated with improved outcomes in FL patients

• The prognostic role of early metabolic response is independent from the type of induction therapy (RB vs RCHOP) and maintenance therapy

We analysed interim metabolic response (iPET) in a subset of Follicular Lymphoma (FL) patients enrolled in the randomized FOLL12 trial. Grade 1-3a FL patients with an iPET performed between cycles 4 and 5 of first-line immunochemotherapy (ICT) were included; PET scan had to be centrally reviewed for the definition of Deauville Score (DS) and were considered positive for DS4-5. Overall 123 patients out of 211 with iPET were available for central review. Of these, 43% were older than 60, 33% had high-risk FLIPI2, and 47% received R-Bendamustine as the induction regimen. iPET showed a complete metabolic response (CMR) in 83% of cases. CMR at the end of induction therapy (eoiPET) was confirmed in 91% of iPET-negative patients. The 5-year PFS was 70% for iPET-negative (95% CI: 60-78%) and 34% for iPET-positive (95% CI: 15-55%) cases (p<0.01). In multivariate analysis, iPET+ was an independent prognostic factor for PFS (HR 2.82, 95% CI: 1.47-5.42). Combining iPET and eoiPET, the 3-year PFS was 78% for both negative iPET and eoiPET, with a reduced risk of progression compared to double-positive cases for double iPET/eoiPET cases. The 5-year OS was 96% for iPET-negative (95% CI: 89-98%) and 85% for DS 4-5 (95% CI: 61-95%), HR 5.74 (95% CI: 1.65-20, p=0.006). Our results confirm that iPET in patients with FL treated with standard ICT is a strong prognostic factor. Assessment of early metabolic response in FL may be considered for defining a novel generation of early response-adapted trials in FL. NCT02063685