Follicular lymphoma treated with first-line immunochemotherapy: a review of PET-CT in patients who did not achieve CMR in the GALLIUM study.

Complete metabolic response (CMR) on positron emission tomography-computed tomography (PET-CT) was the sole independent predictor of overall survival in the PET sub-study of the phase III GALLIUM trial (NCT01332968) in first-line treatment of high tumour burden follicular lymphoma (FL). The aim of this analysis was to investigate further the outcome of patients not achieving CMR. Methods: Two international experts re-reviewed PET-CT scans from patients failing to achieve CMR assessed by the Independent Review Committee (IRC) blinded otherwise to IRC results. Metabolic response category and Deauville score (DS) were assigned. Progression-free survival (PFS) was investigator assessed with contrast-enhanced CT (ceCT). Kaplan–Meier methodology was used to estimate landmark PFS and time-to-next treatment (TTNT) from end-of-induction by DS. Patients who experienced CT-based progressive disease at end-of-induction were excluded. Results: Fifty-four patients were reviewed. Six had CMR, 37 partial metabolic response, two no metabolic response and nine progressive metabolic disease. Patients were reassigned to CMR because fluorodeoxyglucose uptake was considered as i) inflammatory (n = 2), ii) incidental neoplasia (n = 2) or iii) where fluorodeoxyglucose uptake was visually close to liver uptake but quantitatively lower (n = 2). There was a trend for shorter PFS and TTNT for patients with DS-5 than DS-4. High-grade mesenteric uptake at end-of-induction was common, occurring in 20 patients with non-CMR, fourteen of whom achieved CMR at all other sites. Only 3/14 (21%) patients with mesenteric uptake as the only site of disease experienced progression or death within 24 months (PFS24) whereas 4/6 patients (67%) with mesenteric and additional sites of fluorodeoxyglucose-avid disease had a PFS24 event. All patients with early progression had measurable disease on ceCT at fluorodeoxyglucose-avid sites at end-of-induction. Conclusion: After induction immunochemotherapy, CMR was assigned after reassessment in some patients, where increased fluorodeoxyglucose uptake was considered due to inflammation/incidental neoplasia rather than lymphoma. Quantitative assessment to confirm the visual impression of residual uptake in lesions is suggested. Isolated mesenteric fluorodeoxyglucose uptake is likely a common false-positive finding at end-of-induction and does not warrant changes in clinical management nor disease surveillance unless there is measurable disease on ceCT or clinical suspicion of active disease.