Effect of FDG-PET–based bone marrow assessment on prognostic accuracy compared to conventional histologic evaluation in patients with follicular lymphoma: A subanalysis of the FIL FOLL12 trial.

Abstract

7074 Background: Bone marrow biopsy (BMB) is an invasive staging procedure for follicular lymphoma (FL) and its results are needed to calculate FLIPI2 and PRIMA-PI scores. Beyond conventional biopsy bone marrow can also be assessed through FDG-PET bone staging (PETb). We report preliminary data on a comparison of BMB and PETb in assessing BM involvement among FL patients enrolled in the FIL-FOLL12 trial. Methods: Untreated stage II–IV FL patients requiring therapy were included. Patients were balanced according to treatment received and arm. BMBs were assessed by morphology and immunohistochemistry. PET/CT scans were reviewed by two expert nuclear medicine physicians. Pathological bone uptake (PETb+) was defined as mono- or multifocal, or diffuse FDG uptake in bone segments higher than liver activity (SUVmax). Results: This analysis included 179 patients; no significant differences in disease characteristics were observed between the revised cohort and the remaining patients enrolled in the FOLL12 trial. High-risk FLIPI2 was noted in 35.4%, and β2-microglobulin was increased in 53% of patients. BMB involvement was present in 58.5% (median infiltration 30%, range 0.5–95%). PETb was positive in 38 cases (21%), including 14% with focal or multifocal involvement and 7% with diffuse increased uptake. Concordant results between BMB and PETb were observed in 53.6%: among 103 BMB+ patients, 30 were PETb+ (29%). PETb identified BM involvement in 8 cases missed by BMB. While BMB+ was not associated with a different risk of PFS compared to BMB-, we observed a significant impact of PETb+ on PFS: PETb+ had 41% 5-year PFS (CI 25-72, p=0.003), while BMB+/PETb- showed 74% (CI 62-83, p=0.27) and BMB-/PETb- 66%(CI 52-72, reference).We then calculated FLIPI2 and PRIMA-PI using either conventional BMB or PETb to define BM involvement. The agreement between BMB and PETb scores was 87% for FLIPI2 and 67% for PRIMA-PI and the main disagreement was due to reallocation to lower risk groups; FLIPI2 0-2 patients raised from 65% to 74.3% according to FLIPI2-PET. FLIPI2 was confirmed prognostic for PFS and its c-Harrel increased from 0.582 to 0.602 when BMB was substituted with PETb (Table 1), with a 52% (CI 39-64) 5-Year PFS for conventional high risk FLIPI2 shifting to 41% (CI26-56) for high risk FLIPI2-PET. Conclusions: Although BMB detects marrow involvement in most patients, this does not uniformly translate into adverse prognosis. PETb, while less sensitive, identifies metabolically active and prognostically relevant bone disease. A FDG-PET-based assessment of bone involvement could refine risk stratification in FL and spare BMB in most patients Score HR for High risk CI c-Harrell FLIPI2 2.03 1.25-3.31 0.582 FLIPI2-PET 2.58 1.57-4.26 0.602 PRIMA-PI 1.23 0.67-2.23 0.537 PRIMA-PI-PET 1.47 0.85-2.54 0.550