Single-cell RNA sequencing of 1.3 million plasma cells from patients with MGUS and SMM

Introduction: Multiple myeloma (MM) is usually diagnosed in an advanced stage, which is associated with end-organ failure, inferior quality of life and survival, and increased costs for healthcare institutions.MM precursor stages (MGUS and SMM) can be detected easily through blood protein tests.A prospective, nationwide, screening study performed in Iceland, has detected MGUS in 4.9% and SMM in 0.5% of adults >49 years.However, there is still no recommendation regarding the benefits of population screening for MM precursor diseases.The objective of this research is to assess the prevalence of monoclonal plasma cell disorders in the adult population in Uruguay and evaluate the progression to active disease.Methods: A prospective, single-cohort, nationwide descriptive study conducted at Hospital de Clínicas, Montevideo, Uruguay.Residents ≥ 40 years were invited to participate.Recruitment started in October 2021 and ended in October 2022.Patients with a previously known plasma cell disorder were excluded.Medical history was obtained in all cases.CAPILLARYS 2 Flex Piercing was used for Protein and Immunotyping analyses, Hydrasys 2 for immunofixation, and Freelite (The Binding Site) for serum-free light chains.If a monoclonal component (MC) was detected, patients were evaluated according to current IMWG recommendations.Patients diagnosed or progressed to active disease were offered early treatment.Results: 3905 patients were included; the median age was 56 years (40-104) IQR 17, and 58.4% were females.A MC was found in 104 patients (prevalence 2.7%), with a median age of 63 years (40-88) IQR 17, 54.8% were females.Patients without MC had a median age of 55 years (40-104) IQR 17.The median value of the MC was 0.5 g/dl, (0.1-2 g/dl) IQR 0.5.10.6% had a nonquantifiable MC. 3.8% had a bi-clonal MC.MC was IgG 76%, IgA 13.4%, IgM 7.7%, Kappa 1.9%, Lambda 1%.The median value of sFLC kappa, lambda, and ratio (rFLC) were 23.5 mg/L (IQR 24), 18.5 mg/L (IQR 17), and 1.3 (IQR 0.83) respectively.An abnormal rFLC was found in 32% (33/102).Out of 102 patients, 54 were low-risk MGUS, 34 intermediate-low-risk MGUS, 8 intermediatehigh-risk MGUS, 1 SMM, 3 active MM, and 2 asymptomatic Waldenstrom Macroglobulinemia.The patients with active MM had no end-organ failure, and treatment started within 1 month from diagnosis.No significant association was found between MC and gender or comorbidities.1% of patients had a family history of MM.The prevalence of MC according to age subgroups was 1.26% in 40-49 years, 1.92% in 50-59 years, 3.11% in 60-69 years, 6.78% in 70-79 years, and 7.14% in >80 years.Age >55 years was associated with a significant risk of monoclonal gammopathy (OR 2.9; IC 95% 1.87-4.5,p< 0.01).Conclusions: The prevalence of MGUS was 2.45% and SMM was 0.03%.Age >50 years increases significantly the risk of MC. 3 patients were diagnosed with asymptomatic active disease.