Patients with newly diagnosed multiple myeloma (NDMM) exhibit varying outcomes, with around 60% classified as intermediate-risk under the Revised International Staging System (R-ISS). Chromosome 1q gain/amplification (1q+) has recently been identified as a poor prognostic factor. In this study, the European Myeloma Network, through the HARMONY project, collected data from 10,843 patients with NDMM across 16 clinical trials to revise the R-ISS by incorporating additional risk features, including 1q+. An additive scoring system was developed based on top predictors of progression-free survival (PFS) and overall survival (OS) and validated through rigorous analysis.

Researchers identified ISS, del(17p), lactate dehydrogenase, t(4;14), and 1q+ as key factors impacting PFS and OS. These were present in 2,226 patients from the training set (N = 7,072) with a median follow-up of 75 months. Each risk feature was assigned a value based on its impact on OS, leading to the creation of the Second Revision of the International Staging System (R2-ISS). Patients were stratified into four risk groups: low, low-intermediate, intermediate-high, and high, with median OS and PFS significantly differing across these groups. The R2-ISS maintained its prognostic value when validated in an independent set (N = 3,771). This new staging system offers enhanced stratification for intermediate-risk patients with NDMM and can be updated with future prognostic variables.

Reference: D’Agostino M, Cairns DA, Lahuerta JJ, et al. Second Revision of the International Staging System (R2-ISS) for Overall Survival in Multiple Myeloma: A European Myeloma Network (EMN) Report Within the HARMONY Project. J Clin Oncol. 2022;40(29):3406-3418. doi: 10.1200/JCO.21.02614. Erratum in: J Clin Oncol. 2022;40(34):4032. doi: 10.1200/JCO.22.02228.