Impact of 18 f-Fluoro-Deoxyglucose Positron Emission Tomography Imaging in the Management of Mantle Cell Lymphoma
Authors: Bouteloup Juliette , Kanoun Salim , Berriolo-Riedinger Alina , Ghesquières Hervé , Salles Gilles A. , Gargi Thérèse , Mognetti Thomas , Nicolas-Virelizier Emmanuelle , Belhabri Amine , Philippe Rey , Voillat Laurent , Rossi Cedric , Noël Robin , Bastie Jean-Noel M. , Casasnovas Olivier 
Published: October 2019

Abstract
Impact of 18 F-fluoro-deoxyglucose positron emission tomography (PET) imaging has become increasingly important in recent years in the management of patients with malignant lymphomas and is recommended for the staging and response to treatment assessment of both diffuse large B-cell and Hodgkin's lymphoma. Few data on the relevance of PET in the management of patients with mantle cell lymphoma (MCL) are available so far. Then, we retrospectively investigated the PET value for initial staging, interim response and predicting outcome in patients with MCL treated in two French institutions (Dijon University Hospital and the Centre Leon Berard, Lyon).
From 2004 to 2013, a total of 61 de novo MCL patients assessed by PET were included. For each patient, were collected at baseline, the whole body SUVmax site, the presence of a bone marrow (BM) uptake, total metabolic tumour volume (TMTV) and total tumour glycolysis (TLG). The interim PET response after 3 or 4 cycles of induction treatment was assessed using the Deauville score and the quantitative variation of SUV between the baseline PET and the PET performed after 4 cycles of immunochemotherapy (ΔSUV).
Patient's median age was 64 years [38 - 84]. At diagnosis, 92% presented a disseminated disease (stage III-IV). Mean MCL International Prognostic Index (MIPI) was 6.09 [5.89 - 6.29]. All patients received a first-line induction treatment. Twenty-eight (46%) received an autologous stem cell transplantation as consolidation treatment and 10 (16%) a rituximab maintenance. The baseline FDG uptake intensity was low (median SUVmax: 6.93 [2.5 - 25]) leading to consider that baseline PET was informative and suitable for a further PET reassessment in 40 (93%) patients. 72% of the patients with an informative baseline PET, had a SUVmax < 10 making the metabolic quantitative analyses (TMTV, TLG, ΔSUV) uninformative. Among the 46 (75%) patients with histologically proven BM involvement, only 14% of them had BM FDG uptake. After 3 to 4 cycles of induction treatment, 27 (75%) patients achieved a negative PET. With a median follow up of 27 months, a shorter PFS was related to a disseminated disease (stage III-IV) on the basis of baseline PET (2y-PFS: 47% vs 80% p = 0.03) and an insufficient interim metabolic response according to the Deauville score (score ≥ 4) (16% vs 64% p<0.01). However, in multivariate analysis, using the MIPI, the stage and the interim PET response as covariates, only a score of Deauville ≥ 4 (p = 0.0018, HR = 32.6 IC 95% [3.7 - 286.82]) and a MIPI>=6 (p = 0.04, HR = 7.1 IC 95% [1.1 - 46]) retained an independent negative impact on PFS.
FDG avidity of LCM is usually low. PET underestimates BM involvement at diagnosis in 86 % of patients, compared with cytological and histological techniques, and has no independent prognostic value. The interim metabolic response assessed using the Deauville criteria is a prognosis factor independent from MIPI in patients with MCL.

Disclosures
Salles: Calistoga Pharmaceuticals, Inc.; Celgene Corporation; Genentech, Inc.; Janssen Pharmaceutica Products, L.P.; Roche: Consultancy; Celgene Corporation; Roche and Gilead Sciences: Research Funding; Celgene Corporation; Roche: Speakers Bureau. Casasnovas:Gilead: Consultancy; Takeda: Consultancy; Roche: Consultancy, Research Funding.