Increased risk of infections in smoldering multiple myeloma: results from the screened iStopMM study.

Infections are a major cause of morbidity and mortality in multiple myeloma (MM). While increased infection risk has been shown in monoclonal gammopathy of undetermined significance (MGUS), data are limited for smoldering multiple myeloma (SMM). We used data from the iStopMM study, which screened 75,422 Icelandic individuals aged ≥40 years for MM precursors. Individuals diagnosed with SMM were matched by age and sex with MGUS-free comparators (1:5 ratio) and with individuals with MGUS (1:1 ratio). Infection outcomes were derived from nationwide registries of ICD-10 diagnostic codes and antimicrobial prescriptions. Cox proportional hazards models estimated infection risk, adjusted for immunoparesis. 188 SMM individuals were matched to 188 MGUS individuals and 162 SMM individuals were matched to 810 comparators. Individuals with SMM had significantly more infections (HR 1.36, 95% CI 1.07-1.73) and antibacterial prescriptions (HR 1.24, 95% CI 1.01-1.52) than the comparators. Compared to MGUS, individuals with SMM also had more infections (HR 1.37, 95% CI 1.00-1.87). Adjusting for immunoparesis attenuated the associations, suggesting it may partially mediate infection risk. This first screened cohort of SMM shows a significantly increased infection risk, compared to both MGUS and to individuals without MM precursors, suggesting an underrecognized infection burden in SMM.