Prognostic Relevance of 18F-FDG PET/CT In Newly Diagnosed Multiple Myeloma Patients Treated with up-Front Autologous Transplantation: A Prospective Study
Authors: Zamagni Elena , Nanni Cristina , Patriarca Francesca , Tacchetti Paola , Englaro Emanuela , Perrone Giulia , Buttignol Silvia , Brioli Annamaria , Pantani Lucia , Zannetti Beatrice Anna , Caroborante Francesca , Baccarani Michele , Fanti Stefano , Cavo Michele 
Published: October 2019

Abstract
Abstract 369
F-18-fluorodeoxyglucose positron emission tomography integrated with computed tomography (FDG-PET/CT) has been reported to be a careful technique for a widespread screening of myelomatous lesions, both medullary and extramedullary, at the onset of multiple myeloma (MM). By the opposite, the role of FDG-PET/CT in assessing and monitoring response to therapy and the prognostic value of this imaging technique is less explored.
Aim of the present study was to prospectively evaluate the prognostic significance of FDG-PET/CT at diagnosis and after therapy in an homogeneous population of patients with newly diagnosed MM who received up-front single or double autologous stem cell transplantation (ASCT). By study design, all patients were studied with FDG-PET/CT at baseline, 3 months after ASCT, every year during the maintenance/follow-up phase and at time of relapse. Bone marrow involvement was described as negative, diffuse or focal. The number of focal lesions (FL), as well as their size and associated standardized uptake values (SUV) were recorded. Extramedullary disease, if present, was described by location, size, number of lesions and SUV.
A total of 146 patients who actually received the planned treatment program and were followed for a median of 39 months were analyzed. Their median age was 58 years. ISS stage was as follows: 48% stage I, 31% stage II, 14% stage III. Six per cent of the patients had renal failure, related to the presence of hypercalcemia at diagnosis. Del (13q), t(4;14) and del(17p), detected by FISH, were present in 47%, 25% and 10% of the patients, respectively. Induction treatment prior to ASCT included an IMiD in 55% of the patients, bortezomib in 34% and chemotherapy in 11% of the cases.
The best overall response rate, including CR and at least VGPR, was 56% and 82%, respectively. Median PFS of the entire population was 55 months and the 5-year projected OS rate was 85%.
At baseline, 22% of the patients had a negative PET/CT, 27% presented less than 3 FL and 51% 3 or more FL or a diffuse bone marrow uptake of FDG. In 44% of the cases the SUV was low (< 3.9) while in 56% was 4 or more. In 6% of the patients extramedullary disease was present.
No significant differences between patients with positive or negative PET/CT were found regarding baseline characteristics and response to therapy. The entity of PET/CT involvement at baseline influenced clinical outcomes. In particular, patients with more than 3 FL and/or SUV > 3.9 had a significantly shorter OS in comparison with patients with FL < 3 and/or SUV < 3.9 (5-year projected OS: 92% vs 75%, respectively, P=0.04).
After 3 months from ASCT, PET/CT was negative in 65% of the patients and remained positive, either unchanged or with a reduction in the SUV, in 35% of them. A correlation between PET/CT findings and response to ASCT was evident; in particular, among patients with negative PET/CT the rate of CR and VGPR was significantly higher than among patients with positive PET/CT (CR: 68% vs 38%; P= 0.001) (VGPR: 90% vs 76%; P= 0.008). Complete FDG suppression at PET/CT after ASCT conferred superior PFS and OS than persistence of FL (PFS: median 58 vs 45 months, respectively, P=0.05; 5-year projected OS: 92% vs 79%, respectively, P=0.004).
In conclusion, involvement of PET/CT at diagnosis in terms of number of FL and intensity of tumour metabolism (SUV) predicted survival outcome. Complete FDG suppression after ASCT was strictly related with achievement of high-quality response and was prognostically relevant for durable disease control and longer OS.

Disclosures:
Cavo: Jansen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no.