{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:08:00Z","timestamp":1786975680588,"version":"build-2736575974"},"reference-count":14,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"\n Importance<\/jats:title>\n Early treatment may benefit patients with high-risk smoldering multiple myeloma (SMM), a precursor of active multiple myeloma, but inconsistent high-risk definitions may capture different disease subsets.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To compare 2 high-risk SMM risk definitions: the AQUILA trial inclusion criteria and the 2\/20\/20 risk stratification model.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This cohort study included data from 2 separate SMM cohorts and a retrospective analysis assessing progression risk. The Iceland Screens, Treats, and Prevents Multiple Myeloma (iStopMM) is a large population-based screening study in Iceland, conducted from 2016 to 2021, while the Danish Lymphoid Cancer Resource (DALY-CARE) is a nationwide clinical data collection from Denmark from 2002 to 2025. From the iStopMM cohort, individuals with SMM were detected by screening. In DALY-CARE, individuals with SMM were identified in a clinical setting. Data were analyzed from March 2025 to January 2026.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n High-risk SMM by the AQUILA criteria, defined by presence of immunoparesis, monoclonal protein (M-protein) greater than 3.0 g\/dL, immunoglobin A isotype, bone marrow plasma cell infiltration greater than 50%, or free light chain ratio 8 or greater. High risk by the 2\/20\/20 model was defined by presence of more than 1 of: M-protein greater than 2.0 g\/dL, bone marrow plasma cell infiltration greater than 20%, or free light chain ratio greater than 20.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Proportion of high-risk SMM in the 2 cohorts by both models and risk of progression as defined by initiation of treatment.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 193 individuals (median [IQR] age, 70 [63-72] years; 116 [60%] female) from the iStopMM cohort and 1147 individuals (median [IQR] age, 72 [64-79] years; 598 [52%] female) from the DALY-CARE cohort were included. In the screened cohort (iStopMM), 65 participants (34%) had high-risk SMM according to the AQUILA criteria, and 15 participants (8%) had high-risk SMM according to the 2\/20\/20 model. In the clinical cohort (DALY-CARE), 607 participants (55%) met high-risk criteria according to AQUILA, and 219 participants (19%) had high-risk SMM according to the 2\/20\/20 model. For individuals with AQUILA-defined high-risk disease in the clinical cohort, the 2-year progression risk was 27.0% (95% CI, 23.3%-30.7%), with an annual progression rate of 14.5%. For individuals with high risk defined by 2\/20\/20, the 2-year progression risk was 44.1% (95% CI, 37.1%-51.1%), with an annual progression rate of 27.3%.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This cohort study found that the AQUILA trial criteria classified approximately 3 times more patients with SMM as having high risk compared with the 2\/20\/20 model and captured a group with substantially lower progression risk. These results suggest that the 2\/20\/20 model more accurately identifies a truly high-risk group with SMM, for whom early treatment is more likely to be beneficial.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.0831","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T15:30:33Z","timestamp":1776958233000},"page":"653","source":"Crossref","is-referenced-by-count":2,"title":["Identifying High-Risk Smoldering Multiple Myeloma for Early Intervention"],"prefix":"10.1001","volume":"12","author":[{"given":"Cecilie V.","family":"Maeng","sequence":"first","affiliation":[{"name":"Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark"},{"name":"Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark"},{"name":"Danish Cancer Institute, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e6mundur","family":"R\u00f6gnvaldsson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden"},{"name":"Faculty of Medicine, University of Iceland, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Brieghel","sequence":"additional","affiliation":[{"name":"Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark"},{"name":"Danish Cancer Institute, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten N.","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida B.","family":"Kristensen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Odense University Hospital, Odense, Denmark"},{"name":"Department of Clinical Research, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agoston","family":"Szabo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark"},{"name":"Department of Hematology, Vejle Hospital, Vejle, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Gr\u00f8nb\u00e6k","sequence":"additional","affiliation":[{"name":"Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark"},{"name":"Biotech Research and Innovation Center, University of Copenhagen, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten U.","family":"Niemann","sequence":"additional","affiliation":[{"name":"Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark"},{"name":"Danish Cancer Institute, Copenhagen, Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigurdur Y.","family":"Kristinsson","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Iceland, Reykjavik, Iceland"},{"name":"Department of Hematology, Landspitali University Hospital, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigr\u00fan","family":"Thorsteinsd\u00f3ttir","sequence":"additional","affiliation":[{"name":"Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark"},{"name":"Faculty of Medicine, University of Iceland, Reykjavik, Iceland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"2","key":"cbr260004r1","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1038\/s41591-022-02183-6","article-title":"Prevalence of smoldering multiple myeloma based on nationwide screening.","volume":"29","author":"Thorsteinsd\u00f3ttir","year":"2023","journal-title":"Nat Med"},{"issue":"18","key":"cbr260004r2","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.1056\/NEJMoa2409029","article-title":"Daratumumab or active monitoring for high-risk smoldering multiple myeloma.","volume":"392","author":"Dimopoulos","year":"2025","journal-title":"N Engl J Med"},{"key":"cbr260004r3","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.ejca.2022.07.030","article-title":"Lenalidomide-dexamethasone versus observation in high-risk smoldering myeloma after 12 years of median follow-up time: a randomized, open-label study.","volume":"174","author":"Mateos","year":"2022","journal-title":"Eur J Cancer"},{"issue":"11","key":"cbr260004r4","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1200\/JCO.19.01740","article-title":"Randomized trial of lenalidomide versus observation in smoldering multiple myeloma.","volume":"38","author":"Lonial","year":"2020","journal-title":"J Clin Oncol"},{"issue":"15","key":"cbr260004r5","doi-asserted-by":"publisher","first-page":"1658","DOI":"10.1182\/blood.2024025897","article-title":"Efficacy and safety of daratumumab in intermediate\/high-risk smoldering multiple myeloma: final analysis of CENTAURUS.","volume":"145","author":"Landgren","year":"2025","journal-title":"Blood"},{"issue":"8","key":"cbr260004r6","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1016\/S1470-2045(16)30124-3","article-title":"Lenalidomide plus dexamethasone versus observation in patients with high-risk smouldering multiple myeloma (QuiRedex): long-term follow-up of a randomised, controlled, phase 3 trial.","volume":"17","author":"Mateos","year":"2016","journal-title":"Lancet Oncol"},{"issue":"10","key":"cbr260004r8","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/s41408-020-00366-3","article-title":"International myeloma working group risk stratification model for smoldering multiple myeloma (SMM).","volume":"10","author":"Mateos","year":"2020","journal-title":"Blood Cancer J"},{"issue":"5","key":"cbr260004r9","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41408-021-00480-w","article-title":"Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies.","volume":"11","author":"R\u00f6gnvaldsson","year":"2021","journal-title":"Blood Cancer J"},{"key":"cbr260004r10","doi-asserted-by":"publisher","first-page":"131","DOI":"10.2147\/CLEP.S479672","article-title":"The Danish Lymphoid Cancer Research (DALY-CARE) data resource: the basis for developing data-driven hematology.","volume":"17","author":"Brieghel","year":"2025","journal-title":"Clin Epidemiol"},{"key":"cbr260004r11","doi-asserted-by":"publisher","first-page":"583","DOI":"10.2147\/CLEP.S99463","article-title":"The Danish National Multiple Myeloma Registry.","volume":"8","author":"Gimsing","year":"2016","journal-title":"Clin Epidemiol"},{"issue":"9","key":"cbr260004r13","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/s41408-022-00719-0","article-title":"Smoldering multiple myeloma current treatment algorithms.","volume":"12","author":"Rajkumar","year":"2022","journal-title":"Blood Cancer J"},{"issue":"1","key":"cbr260004r14","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1182\/hematology.2022000355","article-title":"The consultant\u2019s guide to smoldering multiple myeloma.","volume":"2022","author":"Thorsteinsdottir","year":"2022","journal-title":"Hematology Am Soc Hematol Educ Program"},{"key":"cbr260004r7","author":"Voorhees","year":"2025"},{"key":"cbr260004r12","unstructured":"Gerds? TA. prodlim: product-limit estimation for censored event history analysis. CRAN: Contributed Packages. Accessed March 30, 2026. https:\/\/cran.r-project.org\/web\/packages\/prodlim\/index.html"}],"container-title":["JAMA Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/articlepdf\/2847979\/jamaoncology_maeng_2026_br_260004_1781656700.78005.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:01:00Z","timestamp":1781794860000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2847979"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,1]]},"references-count":14,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamaoncol.2026.0831","relation":{},"ISSN":["2374-2437"],"issn-type":[{"value":"2374-2437","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6,1]]}}}