Abstract
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.