*2.2. Prognostic Value of 18F-FDG PET*/*CT in MM*

18F-FDG PET/CT is a reliable outcome predictor and is regarded as the elective technique for treatment response evaluation of MM due to its ability to distinguish active from inactive sites of disease [9,12,15]. In newly diagnosed, symptomatic MM patients, three independent PET factors have been recognized to affect both progression-free survival (PFS) and overall survival (OS) in different prospective studies. These parameters are the number of focal, 18F-FDG-avid lesions, the SUVmax of the lesions, and the presence of EMD. Bartel et al. were the first to show in a group of 239 MM patients treated upfront with novel agents and double autologous stem-cell transplantation (ASCT) that the presence of more than three 18F-FDG-avid focal lesions was related to fundamental features of myeloma biology and genomics and was the leading independent parameter associated with inferior PFS and OS [9]. A few years later, in a study by Zamagni et al., including 192 MM patients treated with thalidomide-dexamethasone induction therapy and double ASCT, it was shown that the presence at baseline of at least three focal lesions, a SUVmax > 4.2 of the hottest lesion, and the presence of EMD adversely affected 4-year estimates of PFS, while SUVmax > 4.2 and EMD were also correlated with shorter OS [15]. Further, the IMAJEM study highlighted the role of EMD as an independent, adverse prognostic factor for both PFS and OS in 134 patients receiving a combination of lenalidomide, bortezomib, and dexamethasone with or without ASCT, followed by lenalidomide maintenance [12]. The prognostic significance of the three established PET risk factors was recently confirmed in a prospective study of 48 MM patients treated with induction treatment and ASCT. In that study it was also shown that not only quantitative PET parameters from focal lesions, but also those from reference bone marrow samples, are associated with adverse PFS in the disease [16].

Apart from its predictive role in symptomatic MM, 18F-FDG PET/CT has shown prognostic value in asymptomatic SMM patients. Although existing data are relatively limited, the first published results reflect the potential role of the modality in predicting the risk of progression from SMM to symptomatic disease. Siontis et al. studied a group of 122 SMM patients and found that the 2-year risk of progression to active MM was 75% in patients with a positive PET/CT (with or without lytic lesions), compared to 30% in patients with a negative PET/CT. The median time to progression (TTP) was 21 months for the PET/CT positive group, while the respective TTP for the PET/CT negative group was 60 months [17]. In another prospective, multicentric study of 120 SMM patients and a median follow-up of 2.2 years, patients with a positive PET study without underlying osteolysis had a higher risk of progression to active MM and a shorter TTP than patients who were PET-negative. In particular, 58% of the patients with a positive PET scan progressed to active myeloma in 2 years with a median TTP of 1.1 years, compared to those with a negative PET scan demonstrating a progression rate of 33% and a median TTP of 4.5 years [18].
