Follicular Lymphoma Treated with First-Line Immunochemotherapy: A Review of PET/CT in Patients Who Did Not Achieve a Complete Metabolic Response in the GALLIUM Study

Complete metabolic response (CMR) on PET/CT was the sole inde-pendent predictor of overall survival in the PET substudy of the phase III GALLIUM trial (NCT01332968) in first-line treatment of high-tumor -burden follicular lymphoma. The aim of this analysis was to further investigate the outcome of patients not achieving CMR. Methods: Two international experts rereviewed PET/CT scans from patients fail-ing to achieve CMR assessed by the Independent Review Committee masked otherwise to committee results. Metabolic response category and Deauville score were assigned. Progression-free survival (PFS) was investigator-assessed with contrast-enhanced CT. Kaplan-Meier methodology was used to estimate landmark PFS and time to next treatment from end of induction by Deauville score. Patients who experienced CT-based progressive disease at the end of induction were excluded. Results: Fifty-four patients were reviewed. Six had CMR, 37 had a partial metabolic response, 2 had no metabolic response, and 9 had progressive metabolic disease. Patients were reassigned to CMR because 18F-FDG uptake was considered inflam-matory (n = 2), was considered incidental neoplasia (n = 2), or was visually close to liver uptake but quantitatively lower (n = 2). There was a trend for shorter PFS and time to next treatment for patients with a Deauville score of 5 than a score of 4. High-grade mesenteric uptake at the end of induction was common, occurring in 20 patients with non-CMR, 14 of whom achieved CMR at all other sites. Only 3 of 14 (21%) patients with mesenteric uptake as the only site of disease ex-perienced progression or death within 24 mo, whereas 4 of 6 patients (67%) with mesenteric and additional sites of 18F-FDG-avid disease experienced progression or death within 24 mo. All patients with early progression had measurable disease on contrast-enhanced CT at F-18-FDG-avid sites at the end of induction. Conclusion: After induction immunochemotherapy, CMR was assigned after reassessment in some patients, in whom increased F-18-FDG uptake was considered due to inflammation or incidental neoplasia rather than to lymphoma. Quantitative assessment to confirm the visual impression of residual uptake in lesions is suggested. Isolated mesenteric F-18-FDG uptake is likely a common false-positive finding at the end of induction and does not warrant changes in clinical management or disease surveil-lance unless there is measurable disease on contrast-enhanced CT or clinical suspicion of active disease.