Re-classifying the risk of patients with multiple myeloma using novel staging systems: Results from a nationwide US-based cohort study

02 Feb 2024

The current staging system for myeloma is the standard revised international staging system (R-ISS), which is commonly used for assessing the prognostic outcomes in myeloma, which roughly estimates an overall survival (OS) of 9 years in stage I patients and 3.6 years in stage III patients.1 However, this system does not account for important factors such as chromosome 1 abnormalities (gain 1q or deletion 17p) or the additive effects of multiple high-risk cytogenetic abnormalities such as double- and triple-hit myeloma.1 Similarly, other high-risk factors for MM, including circulating plasma cells, presence of extramedullary disease, disease burden, mutation type, chromosomal abnormalities, clinical phenotype, and gene expression profiling scores, are not accounted for and represented in the current staging system.1

In recent years, novel staging systems such as the second revision of the R-ISS (R2-ISS) and the Mayo Additive Staging System (MASS) have been established. These staging systems incorporate 1q21 gain and account for the presence of multiple high-risk cytogenetic abnormalities.1 They also highlight the presence of 1q21 abnormalities, with an adjustment of 0.5 points in the R2-ISS and 1 point in the MASS.1 Nevertheless, a direct comparison of the clinical performance between the 3 staging systems had never been performed. As such, a nationwide retrospective cohort study based on the Flatiron Health electronic health record database was conducted to compare the performance and prognostic ability of the R-ISS, MASS, and R2-ISS staging systems in a real-world population in the United States (US).1 During the ASH Annual Meeting & Exposition 2023, Dr. Manni Mohyuddin from the Huntsman Cancer Institute at the University of Utah, the US, shared the results from the study.1

Clinical data were obtained from approximately 280 cancer clinics, mostly in community oncology settings, in the US, which included patients who initiated first-line treatment for newly diagnosed myeloma between January 2016 and October 2022.1 The primary endpoint was the real-world OS in patients with newly diagnosed myeloma and the prognostication ability of each staging system, as evaluated by the Harrell’s C-index.1

A total of 497 patients were included in this study.1 Patient characteristics were largely representative of the general MM patient population. The median age of the patients included was 70 years (IQ range: 62-76).1 33.6% of patients had 1q21 abnormalities and 67.5% of patients received triplet combination therapy during induction.1 The majority of patients were not transplanted which was also reflective of the management of myeloma in the community.1 The R-ISS had classified 24.5%, 62.6% and 12.9% of patients as stage I, II, and II respectively, producing a Harrell’s C-index of 0.58.1 Conversely, the MASS staging system classified patients more equally into the 3 stage groups, with most patients being identified as stage II (stage I: 34.0%, stage II: 35.4%, stage III: 30.6%) and yielding a Harrell’s C-index of 0.60.1 For R2-ISS, despite possessing a comparable predictive accuracy with R-ISS and MASS and a Harrell’s C-index of 0.61, the confidence intervals of the hazard ratio overlapped for stagesI to II and III to IV.1 However, patients categorized as R2-ISS stage II were less likely to experience stage migration from R-ISS, indicating R2-ISS’s capability in re-categorizing patients into more refined prognostic subsets.1

In conclusion, novel staging systems such as the R2-ISS and MASS perform similarly in the US.1 These staging systems re-classify R-ISS stage II MM patients into more refined prognostic subsets.1 Long-term follow-up and assessments of these staging systems are further required.1

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