利用动态生物标志物对冒烟型多发性骨髓瘤进行强化风险分层：一项纳入2270名参与者的多国多中心研究（PANGEA 2.0）。

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

作者信息

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

机构信息

Angers University Hospital.

Dana-Farber Cancer Institute.

出版信息

Res Sq. 2025 Jun 3:rs.3.rs-6696313. doi: 10.21203/rs.3.rs-6696313/v1.

DOI:10.21203/rs.3.rs-6696313/v1

PMID:40502745

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12155220/

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).

摘要

准确预测冒烟型多发性骨髓瘤（SMM）进展为活动性多发性骨髓瘤（MM）的风险，对于制定个体化早期治疗策略、降低过度治疗风险至关重要。目前的风险分层模型未考虑生物标志物轨迹的动态变化。我们汇集了来自六个国际中心的2270例SMM患者的最大队列，这些患者具有纵向临床和生物学数据，用于训练和验证PANGEA 2.0风险模型。四种动态变化的生物标志物与较短的疾病进展时间显著相关：M蛋白增加≥0.2g/dL、受累：未受累血清游离轻链比值增加≥20、肌酐增加>25%以及血红蛋白降低≥1.5g/dL。PANGEA 2.0在预测疾病进展方面比包括20/2/20和国际骨髓瘤工作组（IMWG）模型在内的现有模型表现更优（C统计量=0.69 - 0.84），即使没有生物标志物病史（C统计量=0.69 - 0.83）或近期骨髓活检结果。PANGEA 2.0是一个易于使用的开放获取工具（https://ghobrial.shinyapps.io/pangea_2_calculator），可用于改进和个体化SMM风险分层。还有验证工具可用于将PANGEA 2.0与现有模型进行比较（https://ghobrial.shinyapps.io/pangea_validation）。