Baseline Suvmax Did Not Predict Histological Transformation from Follicular Lymphoma to Aggressive Lymphoma in the Phase III GALLIUM Study
Authors: Mir Farheen , Barrington Sally F , Meignan Michel , Brown Helen , Nielsen Tina , Sahin Deniz , Trotman Judith 
Published: October 2019

Abstract
Introduction: Follicular lymphoma (FL) generally has an indolent clinical course, but there is a 1-2% annual rate of histological transformation (HT) into aggressive lymphoma. Nodal HT sites have a higher maximum standardized uptake value (SUVmax) than non-transformed sites, and patients with HT typically show greater variation in SUVmax between sites. Upfront identification of patients at high risk of HT would allow physicians to consider treatment intensification. The objective of this analysis was to assess the relationship between baseline SUVmax (bSUVmax) and HT in the GALLIUM study (NCT01332968).
Methods In the randomized, phase III GALLIUM study, 1202 previously untreated patients with grade 1-3a FL were randomized to receive induction with either obinutuzumab (GA101; G)- or rituximab (R)-based immunochemotherapy. Patients who responded received maintenance therapy with the same antibody. The primary endpoint of investigator-assessed progression-free survival was significantly improved in the G arm relative to the R arm (hazard ratio 0.66; p=0.001). As an exploratory endpoint, the degree of 18-fluorodeoxyglucose (FDG)-avidity expressed by SUVmax was assessed in patients with baseline FDG positron emission tomography (FDG-PET) scans by an independent review committee.
Results: Among 522 patients with available bSUVmax data, 13 (2.5%) experienced biopsy-confirmed HT to diffuse large B-cell lymphoma or Grade 3b FL after a median follow-up of 59 months. Patients with HT were older (median age 61 vs 56 years), and were more likely to have a poor performance status (Eastern Cooperative Oncology Group [ECOG] performance status 2: 15.4% vs 2.6%), present with high-risk Follicular Lymphoma International Prognostic Index (FLIPI; 61.5% vs 40.3%), and have bone marrow involvement (76.9% vs 52.9%) than those without. More than 65% of patients showed bSUVmax >10, but only a minority of these experienced HT. Median (range) bSUVmax in patients with versus without HT was 12.4 (8.14, 27.95) versus 11.8 (3.05, 64.43), respectively. Median (range) baseline SUVrange (bSUVrange), defined as the difference between bSUVmax of the most and least FDG-avid lymphoma sites, was 6.6 (1.08, 23.91) versus 7.14 (0.00, 59.81), respectively (Figure).
Conclusions: bSUVmax >10 is common in patients with previously untreated FL and is rarely associated with early HT. Neither bSUVmax nor bSUVrange predicted HT in GALLIUM, suggesting there may be little benefit in re-biopsy of lesions to exclude HT before commencing therapy. Better markers for identification of FL patients at risk of transformation are needed.

Disclosures
Mir: F. Hoffmann-La Roche: Employment. Barrington:F.Hoffmann-La Roche: Membership on an entity's Board of Directors or advisory committees; Department of Health (England): Research Funding; MRC: Research Funding; CRUK: Research Funding; EPSRC: Research Funding; National Institute of Health Research: Research Funding. Meignan:F. Hoffman-La Roche Ltd: Honoraria. Brown:PAREXEL, external business partner with Roche Products Ltd, Welwyn, UK: Employment. Nielsen:F. Hoffmann-La Roche Ltd: Employment, Other: Ownership interests PLC. Sahin:F. Hoffman-La Roche Ltd: Other: Ownership interests PLC. Trotman:F. Hoffman-La Roche: Other: Travel to meeting, Unremunerated member of Ad Board, Research Funding; Janssen: Other: Unremunerated member of Ad Board, Research Funding; Beigene: Research Funding; Takeda: Other: Unremunerated member of Ad Board; Celgene: Other: Unremunerated member of Ad Board, Research Funding; PCYC: Research Funding.