Brieghel Christian, Slørdahl Tobias Schmidt, Andersen Morten Nørgaard, Szabo Agoston Gyula, Niemann Carsten Utoft, Thorsteinsdóttir Sigrún
Department of Hematology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
Hematology Branch, Danish Cancer Institute, Copenhagen, Denmark.
Blood Cancer J. 2025 Apr 7;15(1):59. doi: 10.1038/s41408-025-01268-y.
The revised international staging system (R-ISS) in multiple myeloma (MM) was recently updated as the second R-ISS (R2-ISS) and refined prognostication in clinical trial populations. By including 2929 Danish patients with MM and complete data on R2-ISS registered from 2005 through 2019, we validated the R2-ISS for overall survival (OS) in a population-based cohort; however, only partly among younger patients. We thus developed a real-world international staging system (RW-ISS) from a 75% training cohort. Feature selection and weighted scores of high-risk variables from a Cox regression model of OS included age >70 years (2 points), performance status (PS) > 1 (2 points), PS 1 (1 point), t(14;16) (1 point), ISS III (1 point), ISS II (0.5 points), high lactate dehydrogenase (0.5 points), and del(17p) (0.5 points). In the test set, patients with RW-ISS I (0-2.0 points, 38.2%), II (2.5-3.0 points, 19.8%), III (3.5-4.5 points, 27.1%), and IV (5.0-7.0 points, 15.0%) demonstrated a median OS of 9.5, 5.5, 3.4, and 1.1 years, respectively (P < 0.0001) and the C-index was superior for RW-ISS as compared to both R2-ISS and R-ISS (0.708 vs 0.604 vs 0.595, respectively). RW-ISS was in part externally validated. We thus recommend using RW-ISS in routine clinical care of NDMM.
多发性骨髓瘤（MM）的修订国际分期系统（R-ISS）最近更新为第二代R-ISS（R2-ISS），并在临床试验人群中优化了预后评估。通过纳入2929例丹麦MM患者，并获取2005年至2019年登记的完整R2-ISS数据，我们在一个基于人群的队列中验证了R2-ISS对总生存期（OS）的评估；然而，仅在部分年轻患者中得到验证。因此，我们从75%的训练队列中开发了一个真实世界国际分期系统（RW-ISS）。从OS的Cox回归模型中进行特征选择和高风险变量加权评分，包括年龄>70岁（2分）、体能状态（PS）>1（2分）、PS 1（1分）、t(14;16)（1分）、ISS III（1分）、ISS II（0.5分）、高乳酸脱氢酶（0.5分）和del(17p)（0.5分）。在测试集中，RW-ISS I（0 - 2.0分，38.2%）、II（2.5 - 3.0分，19.8%）、III（3.5 - 4.5分，27.1%）和IV（5.0 - 7.0分，15.0%）的患者中位OS分别为9.5年、5.5年、3.4年和1.1年（P < 0.0001），与R2-ISS和R-ISS相比，RW-ISS的C指数更高（分别为0.708、0.604和0.595）。RW-ISS在一定程度上得到了外部验证。因此，我们建议在新诊断MM的常规临床护理中使用RW-ISS。
