Enhanced Risk Stratification of Smoldering Multiple Myeloma with Dynamic Biomarkers: A Multinational, Multicenter Study including 2,270 Participants (PANGEA 2.0).

Journal: Research Square
Published:
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).

Authors
Floris Chabrun, Daniel Schwartz, Susanna Gentile, Elias Mai, Tulika Gupta, Jacqueline Perry, David Cordas Santos, Thomas Hielscher, Annika Werly, Sophia Schmidt, Foteini Theodorakakou, Despina Fotiou, Christine Liacos, Nikolaos Kanellias, Noelia Gisbert, Esperanza Martin Sanchez, Rosalinda Termini, Johannes Waldschmidt, Selina Chavda, Louise Ainley, Matteo Claudio Vià, Claudio De Magistris, Loredana Pettine, Michael Timonian, Jean-baptiste Alberge, Vidhi Patel, Patrick Costello, Catherine Tobia, Sally Phan, Jennifer Lamb, Maria-theresa Silverio, Maya Davis, Elizabeth O'donnell, Catherine Marinac, Omar Nadeem, Niccolo Bolli, Kwee Yong, Martin Kortüm, Hermann Einsele, Maria Victoria Manteca, Shaji Kumar, Jesus Miguel, Bruno Paiva, Efstathis Kastritis, Meletios Dimopoulos, Marc Raab, Lorenzo Trippa, Irene Ghobrial