The Early Benefits and Psychological Effects of Screening for Monoclonal Gammopathy of Undetermined Significance: Results of the Istopmm Study

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.214-214
• Main Authors: Rögnvaldsson, Sæmundur, Thorsteinsdottir, Sigrun, Oskarsson, Jon, Eythorsson, Elias, Sigurdardottir, Gudrun Asta, Vidarsson, Brynjar, Onundarson, Pall T., Agnarsson, Bjarni, Sigurdardottir, Margret, Olafsson, Isleifur, Thorsteinsdottir, Ingunn, Bjornsson, Andri Steinthor, Wessman, Inga Dröfn, Gislason, Gauti, Sigurdsson, Jon Kristinn, Olafsson, Andri, Sverrisdottir, Ingigerdur, Long, Thorir E., Palmason, Robert, Sveinsdottir, Signy Vala, Sigurdsson, Fridbjorn, Thordardottir, Asdis Rosa, Jonsson, Asbjorn, Palsson, Runolfur, Indridason, Olafur, Reed, Elin Ruth, Hakonardottir, Gudlaug Katrin, Steingrimsdottir, Hlif, Hultcrantz, Malin, Durie, Brian GM, Harding, Stephen J., Aspelund, Thor, Landgren, Ola, Love, Thorvardur Jon, Kristinsson, Sigurdur Y.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-186397

Introduction: Multiple myeloma (MM) develops over years from the asymptomatic precursors, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Recent evidence shows that initiating treatment at an asymptomatic stage improves outcomes in MM. However, a vast majority of MM patients are diagnosed at the point of symptomatic malignancy and never have the opportunity to receive early treatment. We aimed to evaluate systematic screening for MGUS as a way to significantly expand the availability of early treatment and improve overall outcomes. Despite the widespread use of cancer screening, the literature on the potential harms of screening, particularly psychological harms, is limited. Studies on the psychological effects of screening are therefore, urgently needed. The Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM) is a population-based screening study and randomized controlled trial (RCT) of follow-up strategies aimed at evaluating the potential benefits and harms of MGUS screening. Methods: All residents of Iceland born in 1975 or earlier were invited to participate of whom 80,759 individuals (54% of the eligible population) provided written informed consent for screening. Serum samples collected between 2016-2020 were screened by serum protein electrophoresis (SPEP) and free light-chain (FLC) assay. Those who had MGUS entered a RCT of follow-up strategies. Arm 1 was not notified; Arm 2 was followed according to guidelines; Arm 3 was followed according to a more intensive strategy. Participants who progressed were offered early treatment. Participants were followed to a diagnosis of MM, SMM, Waldenström's macroglobulinemia (WM), smoldering WM, chronic lymphocytic leukemia (CLL), and non-Hodgkin's lymphoma (NHL) with censoring at death. Progression rates were compared using the log-rank test. At registration, all participants were asked to answer the Patient Health Questionnaire 9 (PHQ-9), General Anxiety Disorder 7 (GAD-7), and the Satisfaction with Life Scale (SWLS), validated questionnaires that assess depression, anxiety, and satisfaction with life. These questionnaires were sent annually to all participants and two weeks after MGUS diagnosis to Arms 2 and 3. Scores for Arm 1 and Arms 2 and 3 combined were compared using a generalized estimating equations linear model to account for multiple and differential numbers of observations before and after MGUS diagnosis. Results: A total of 75,422