Sars-Cov-2 Infection Does Not Lead to Progression of Monoclonal Gammopathy of Undetermined Significance: Results from the Population-Based Istopmm Screening Study

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.4766-4766
• Main Authors: Palmason, Robert, Ekberg, Sara, Eythorsson, Elias, Rögnvaldsson, Sæmundur, Thorsteinsdottir, Sigrun, Crowther, Michael, Reed, Elin Ruth, Oskarsson, Jon, Sigurdardottir, Gudrun Asta, Aspelund, Thor, Vidarsson, Brynjar, Onundarson, Pall T., Agnarsson, Bjarni, Sigurdardottir, Margret, Thorsteinsdottir, Ingunn, Sveinsdottir, Signy Vala, Olafsson, Isleifur, Thordardottir, Asdis Rosa, Jonsson, Asbjorn, Indridason, Olafur, Gislason, Gauti, Olafsson, Andri, Sigurdsson, Jon Kristinn, Steingrimsdottir, Hlif, Long, Thorir E., Hultcrantz, Malin, Durie, Brian GM, Harding, Stephen J., Landgren, Ola, Palsson, Runolfur, Love, Thorvardur Jon, Kristinsson, Sigurdur Y.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-173078

Background The mechanisms that lead to the progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM) and related disorders are largely unclear. Infections have been hypothesized to play a role in the onset of MM through dysregulation of the immune response or chronic immune stimulation. Therefore, the effect of concurrent viral infection, for example SARS-CoV-2 infection, might increase the risk of MGUS progression to MM. In Iceland, widespread and easy access to PCR testing for SARS-CoV-2 was implemented early in the COVID-19 pandemic, leading to very high testing rates. This provides a unique opportunity to evaluate whether PCR-proven SARS-CoV-2 infection has an impact on the risk of MGUS progression. To study this relationship, we performed a prospective nationwide study based on data from the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study. Methods A total of 75,422 individuals were screened for M protein and free light chains (FLC) between September 2016 and December 2020, and 3,358 individuals were diagnosed with MGUS and randomized to one of three study arms, two of which (n=2,037) are followed longitudinally with repeated serum protein electrophoresis (SPEP) and FLC analysis. These two arms comprised the study population. Iceland enforced a strict COVID-19 screening policy at the beginning of the pandemic where individuals suspected of having SARS-CoV-2 infection, exposed to SARS-CoV-2, or as part of a screening program underwent PCR testing. This screening policy ended on February 23 rd, 2022. All PCR test results in Iceland (positive or negative) and SARS-CoV-2 vaccinations were centrally registered, providing complete nationwide information on SARS-CoV-2 infections and vaccination coverage. By cross linking this data to the iStopMM database, individuals with MGUS who underwent PCR testing for SARS-CoV-2 in Iceland were identified. As M protein levels change over time, a linear mixed model with random intercept and slope was used to estimate changes in M protein concentration as a function of age, before and after SARS-CoV-2 infection. The slope of the evolution of M protein level over age was modelled using a restricted cubic spline to determine the effects of a proven infection on changes in M protein levels. Results A total of 1,305 individuals (53% males) with MGUS who had undergone at least one PCR test for SARS-CoV-2 were identified. Median age was 66 years (range: 41-97) and m