Monoclonal Gammopathy of Undetermined Significance and Risk of Infections: A Population-Based Study

Based on clinical case reports and small hospital-based patient series, monoclonal gammopathy of undetermined significance (MGUS) has been reported to increase morbidity due to bacterial infections; however, no comprehensive evaluation has been conducted.

Using population-based data from Sweden, we assessed the risks of viral and bacterial infections (reported to the Patient-Registry) in 5,326 MGUS patients diagnosed 1958–2006, compared to 20,161 matched population-based controls. We fit Cox proportional hazard models to estimate hazard ratios (HRs) as measures of risk.

At 5 years of follow-up MGUS patients had a 2.1-fold (95% confidence interval (CI) 2.1–2.3) increased risk of developing any infection compared to controls; at 10 years of follow-up, the risk was very similar (HR=2.2; 95% CI 2.0–2.3). MGUS patients had a 2.2-fold (95% CI 2.0–2.4) and 2.1-fold (95% CI 2.0–2.3) increased risk of developing bacterial infections at 5 and 10 years, respectively. A significantly increased risk (P<0.05) was found for pneumonia, osteomyelitis, septicemia, pyelonephritis, cellulitis, endocarditis and meningitis. We also assessed the risk of developing viral infections; compared to controls, MGUS patients had a 2.7-fold (95% CI 2.2–3.3) and 2.9-fold (95% CI 2.3–3.7) increased risk at 5 and 10 years, respectively, with a significantly increased risk for influenza and herpes infections (P<0.05). Risk of infections did not differ by MGUS isotype. MGUS patients with an M-protein >2.5 g/dL at diagnosis had higher risks of infections compared to those <0.5 g/dL. However, compared to controls the risk of infections was also significantly increased among MGUS patients with a concentration <0.5 g/dL. MGUS patients with (versus without) infections had no excess risk of developing multiple myeloma or related malignancies.

Based on over 5,000 MGUS patients, we found a 2-fold higher risk of developing bacterial and viral infections, compared to controls. The risk was highest among MGUS patients with high M-protein concentrations at diagnosis (>2.5 g/dL); however, the risk was still significantly increased among those with a concentration <0.5 g/dL. Infections in patients with MGUS were not associated with an increased risk of malignant transformation. We recently showed that patients with MGUS have a 3-fold risk of death in bacterial infections. Our findings may have clinical implications for treatment strategies and prophylactic measures, as well as surveillance of MGUS patients.

No relevant conflicts of interest to declare.