Prevalence of Monoclonal Gammopathies in Adult Uruguayan Population

Introduction: The incidence of Multiple myeloma (MM) is increasing worldwide due to the ageing population. Substantial improvements in survival rates have been demonstrated over the past decade, primarily attributed to the advent of novel targeted therapies and improvements in supportive care treatment. 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. In Uruguay, 87% of MM patients are diagnosed with organ damage. MM precursor stages (MGUS and SMM) can be detected easily through blood protein tests. A prospective, nationwide screening study performed in Iceland has reported a prevalence of MGUS of 4.9% and SMM of 0.5% in adults > 49 years. However, there is still no universal recommendation regarding the benefits of population screening for MM precursor diseases.

Aim: 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. Uruguayan inhabitants ≥ 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 according to standard guidelines.

Results:

3905 patients were recruited; 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) IQ 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 non-quantifiable MC, and 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 FLCr was found in 32% (33/102).

Regarding the immunophenotype, the median proportion of abnormal/normal plasma cells was 32.75% for MGUS (0-79 [IQR 60.75]) and 97.5% for patients with MM (95-98 [IQR 2.88]), with a statistically significant difference (p<0.001).

Out of 102 patients, 54 were low-risk MGUS, 34 intermediate-low-risk MGUS, 8 intermediate-high-risk MGUS, 1 SMM, 3 active MM, and 2 asymptomatic Waldenström Macroglobulinemia. The patients with active MM had no organ damage, and they started treatment within 1 month from diagnosis. No significant association was found between MC and gender or comorbidities (hipertension, diabetes, autoimmune disorders). 1% of patients had a family history of MM. Of the symptoms investigated in the initial questionnaire, only weight loss was associated with a statistically significant difference between patients with and without PM (p<0.001).

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 that of SMM was 0.03%. Age > 50 years was significantly associated with an increased risk of MC. Three patients were diagnosed with asymptomatic active disease and benefited from early treatment, having no organ damage at the time of diagnosis. According to our results, 38 persons need to be studied to detect one positive patient. At a median follow-up of 22.5 months, four patients died from causes unrelated to the monoclonal gammopathy, while the remaining patients did not exhibit any disease progression.

No relevant conflicts of interest to declare.