Multiple Myeloma (MM) is rare in young patients - especially before 40 years at diagnosis, representing less than 2% of all patients with MM. Little is known about the disease characteristics and prognosis of these patients. In this study we examined 214 patients diagnosed with MM ≤ 40 years old over 15 years, in the era of modern treatments. Among them, 189 patients had symptomatic MM. Disease characteristics were similar to older patients: 35% had anemia, 17% had renal impairment, and 13% hypercalcemia. The staging was ISS-1 in 52.4%, ISS-2 in 27.5% and ISS-3 in 20.1%. Overall, 18% of patients had high risk cytogenetics (del 17p and/or t(4;14)). Ninety percent of patients received intensive chemotherapy followed by autologous stem cell transplant, and 25% of patients had allogeneic stem cell transplantation predominantly at time of relapse. The median follow-up was 76 months, the estimated median overall survival was 14.5 years and the median PFS was 41 months. In multivariate analysis, bone lesions (HR=3.95; p=0.01), high ISS score (HR=2.14; p=0.03) and high-risk cytogenetics (HR=4.54; p<0.0001) were significant risk factors for poor outcomes. Among predefined time-dependent covariables, onset of progression (HR=13.2; p<0.0001) significantly shortened OS. At 5 years, Relative Survival compared to same age and sex matched individuals was 83.5%, and estimated Standardized Mortality Ratio was 69.9 (95%CI 52.7-91.1), confirming that MM dramatically shortens the survival of young patients despite an extended survival after diagnosis.

Background: Multiple myeloma is a hematological neoplasm characterized by a clonal proliferation of malignant plasma cells in the bone marrow, and is associated with high morbidity and mortality and variable survival. Positron emission tomography combined with computed tomography using 18F-deoxyfluoroglucose (FDG-PET/CT) is a promising technique for initial staging of symptomatic multiple myeloma patients. The objective of this study was to assess the prognostic value of this technique at baseline in symptomatic multiple myeloma patients included in two large European prospective studies (French and Italian). Methods: We retrospectively performed a combined harmonized analysis of 227 newly diagnosed transplant eligible multiple myeloma patients from two separate phase III trials. All images were centrally reviewed and analyzed using visual criteria and maximal standardized uptake value. An ad-hoc approach (called modified Combat) was applied to harmonize the data and then remove the “country effect” in order to strengthen the reliability of the final conclusions. Results: Using a multivariate analysis including treatment arm, R-ISS score, presence of extra-medullary disease and bone SUVmax, only bone SUVmax (p = 0.016) was an independent prognosis factor with an OS threshold of 7.1. For PFS, treatment arm and presence of extra-medullary disease were both independent prognosis biomarkers (p = 0.022 and 0.006 respectively). Conclusions: Our results show that bone SUVmax is a simple and reliable biomarker to analyze FDG-PET/CT at baseline that strongly correlates with a poorer prognosis for MM patients.

Multiple myeloma (MM) is a haematological neoplasm characterized by a clonal proliferation of malignant plasma cells in the bone marrow. MM is associated with high morbidity and mortality and variable survival, which can be very short for some patients but over 10 years for others. These differences in survival are explained by intra- and inter-tumoral heterogeneity and demonstrate the potential benefits of adapting the treatment course for high-risk patients with a poorer prognosis. Indeed, identification of these high-risk patients is necessary and is based on the identification of high-risk biomarkers including clinical variables, genomics and imaging results. Positron emission tomography combined with computed tomography using 18F-deoxyfluoroglucose (FDG-PET/CT) is a reliable technique for the initial staging of patients with symptomatic multiple myeloma (MM), and has been included in the IMWG (International Myeloma Working Group) recommendations in 2019. According to clinical studies, FDG-PET/CT characteristics could be used to define high-risk patients at initial diagnosis of symptomatic MM. The goal of this review is to demonstrate the prognostic value of FDG-PET in symptomatic MM patients, particularly in identifying high-risk patients, and thus, to best adapt therapeutic management in the future.