Year: 2026
Type: article
Study design: Observational Study
Abstract: Accurate prediction of risk of progression from smoldering (SMM) to active multiple myeloma (MM) is paramount to individualized early therapeutic strategies with minimum risk of overtreatment. Current risk stratification models do not account for evolving biomarker trajectories. We assembled the largest cohort to date of 2,270 SMM patients from six international centers with longitudinal clinical and biological data to train and validate the PANGEA 2.0 risk models. Four evolving biomarkers were significantly associated with shorter time-to-progression: M-protein increase ≥0.2g/dL, involved:uninvolved serum free light chain ratio increase ≥20, creatinine increase >25%, and hemoglobin decrease ≥1.5g/dL. PANGEA 2.0 outperforms established models including the 20/2/20 and IMWG models by more accurately predicting progression (C-statistics=0.69-0.84), even without biomarker history (C-statistics=0.69-0.83) or recent bone marrow biopsy. PANGEA 2.0 is an easy-to-use, open-access tool (https://ghobrial.shinyapps.io/pangea_2_calculator) to improve and individualize SMM risk stratification. Validation tools are available to compare PANGEA 2.0 to established models (https://ghobrial.shinyapps.io/pangea_validation).
Source: Nature Medicine
Authors: Floris Chabrun, Daniel E. Schwartz, Susanna Gentile, Elias K. Mai, Tulika R. Gupta, Jacqueline Perry, David M. Cordas dos Santos, Thomas Hielscher, Annika Werly, Sophia K. Schmidt, Foteini Theodorakakou, Despina Fotiou, Christine Ivy Liacos, Nikolaos Kanellias, Noelia Collado Gisbert, Esperanza Martin-Sanchez, Rosalinda Termini, Johannes Waldschmidt, Selina J. Chavda, Louise Ainley, Matteo Claudio Da Vià, Claudio De Magistris, Loredana Pettine, Michael A. Timonian, Jean-Baptiste Alberge, Vidhi Patel, Patrick Costello, Catherine Tobia, Sally Phan, Jennifer Lamb, Maria-Theresa Silverio, Maya Davis, Elizabeth K. O’Donnell, Catherine R. Marinac, Omar Nadeem, Niccolo Bolli, Kwee Yong, K. Martin Kortüm, Hermann Einsele, María-Victoria Mateos, Shaji Kumar, Jesús F. San-Miguel, Bruno Paiva, Efstathios Kastritis, Meletios A. Dimopoulos, Marc S. Raab, Lorenzo Trippa, Irene M. Ghobrial
Institutions: Harvard University, Dana-Farber Cancer Institute, Université d'Angers, Massachusetts General Hospital, Sapienza University of Rome, University Hospital Heidelberg, Yale University, German Cancer Research Center, National and Kapodistrian University of Athens, Navarre Institute of Health Research, Clinica Universidad de Navarra, Centro de Investigación Médica Aplicada, University of Würzburg, Universitätsklinikum Würzburg, University College London, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Broad Institute, University of Milan, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer, Mayo Clinic, Mayo Clinic Comprehensive Cancer Center (Minnesota), Korea University, Dana-Farber/Harvard Cancer Center
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: Amgen, Bristol-Myers Squibb, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Massachusetts General Hospital, Yale University, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Celgene, Karyopharm Therapeutics, Deutsches Krebsforschungszentrum, Regeneron Pharmaceuticals, Università degli Studi di Milano, Broad Institute, Prothena, Menarini Silicon Biosystems, Adaptive Biotechnologies, BeiGene, Cancer Research UK, University College London, European Commission, Deutsche Forschungsgemeinschaft, Korea University, Ligue Contre le Cancer, Sapienza Università di Roma, Universidad de Navarra, Associazione Italiana per la Ricerca sul Cancro, National and Kapodistrian University of Athens, Genesis Pharma, Universite Angers, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Regione Lombardia, Centro de Investigación Biomédica en Red de Cáncer, Universitätsklinikum Heidelberg, Aptitude Health, Fondazione Regionale per la Ricerca Biomedica, CRIS Cancer Foundation, National Institutes of Health, Instituto de Salud Carlos III, National Cancer Institute, Cilag
Awards: G1280267364, G2370590264, G2424557443, G2559588348, Adipositasassoziierte Metaflammation als Treiber der Transition von Myelom Vorerkrankungen zur symptomatischen Erkrankung, G434337789, G537148370, Elucidation of risk factors and health determinants associated with PROGRESSION of Monoclonal Gammopathies to Multiple Myeloma, G5697690356, Inmunomonitorización de nueva generación en mieloma múltiple, G8352936557, G8486413159, G8820069626, Training Grant in Quantitative Sciences for Cancer Research, Molecular prediction of myeloma in African Americans
OpenAlex ID: W7140170684