Secure: A Prospective Long-Term Observational Study in Patients with Monoclonal Gammopathy of Undetermined Significance

• Published in: Blood 2024-11, Vol.144 (Supplement 1), p.6889-6889
• Main Authors: Ramasamy, Karthik, Knight, Elizabeth, Byun, Sulgi, Heartin, Earnest, Garvey, Victoria, Basu, Supratik, Stones, Jacqueline, Oakes, Roderick, Killingsworth, Grace, Nicholls, Patricia, Mahmood, Samiya, Bowcock, Stella, Ryan, Rachel, Essex, Sarah, Alfred, Arun, Collier, Dawn, De soysa, Lally, Bradley, Rachel, Thomas-Dewing, Rowena, Cawley, Kathryn, Kaczmarski, Richard, Al-Obaidi, Magda, Cubos, Freter, Bomken, Charlotte, Stern, Simon, Elonen, Tiina, Raymode, Parizade, Chathurani, Dinusha, Jenkins, Louise, Bygrave, Ceri, Garcia Consuegra, Roberto, Harrison, Wendy, Willis, Fenella, Brouwer, Richard, Koshiaris, Constantinos, Vallance, Grant, Gamble, Vicki, Javaid, Kassim, Sadler, Ross, Pratt, Guy
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-203107

Background and Significance: Monoclonal gammopathy of undetermined significance (MGUS) is a precursor to multiple myeloma (MM), affecting approximately 3.2% of people over 50 years old. Whilst about 1% of MGUS cases progress to MM annually, most are asymptomatic and detected incidentally, leading to inconsistent management and follow-up practices. The SECURE study aims to address gaps in understanding routes to diagnosis, risk factors of MGUS progression and psychological effects of living with an MGUS diagnosis. This study will generate prospective data to fill these gaps in the literature. Study Design and Methods: SECURE is a national longitudinal observational study set to recruit 2000 MGUS patients from over 30 NHS sites across the UK. Recruitment started in September 2023 and is planned to end in December 2025, with each participant followed for 60 months. Data collection will conclude in December 2030, and final analysis will be completed by December 2031. Patients with MGUS aged 18 or older will be invited to participate and provide informed consent. Exclusion criteria include i) patients with a light chain ratio of 0.3 to 3.0 without monoclonal protein on serum electrophoresis or immunofixation, and ii) those with rapidly rising M-protein or serum free light chains (FLC) indicative of myeloma at diagnosis. Data collection involves baseline assessments, annual questionnaires, bone marrow and blood samples analysed and stored at the Botnar Research Centre, University of Oxford. Recruitment is ongoing across 21 NHS sites in England and Wales, with 254 patients enrolled as of July 2024. Early data cut of 134 risk-stratified patients show a median age of 71 years (range 35-91), of which 53% are male, and 88.8% are of White ethnicity. Risk factors for MGUS progression were noted in 34 (25%) patients with a M-protein value ≥15 g/L, 85 (63.4%) with an abnormal FLC ratio, and 49 (36.6%) patients with non-IgG type MGUS. Risk stratification shows 22 (16.4%) patients at low risk, 55 (41%) at low-intermediate risk, 44 (32.8%) at high-intermediate risk, and 3 (2.2%) at high risk of disease progression. The primary outcome is the incidence rate of MM during the follow-up period. Secondary objectives include MGUS monitoring patterns, incidence of MGCS, routes of MGUS diagnosis, family linkage, quality of life change, and psychological effects. Exploratory endpoints will include health resource utilisation and identifying biochemical and genomic predictive biomark