Table 1.
MM classification systems and definitions of high-risk disease.
| Classification system | Features | Model | Year introduced | References |
|---|---|---|---|---|
| Durie-Salmon | Stage III One or more of the following: hemoglobin <8.5 g/dL; serum calcium >12 mg/dL; Advanced lytic bone lesions; high M-component production rates IgG value>7 g/dL, IgA >5 g/dL; urine light chain M-component >12 g/24 h | Tumor Burden/Stage | 1975 | Durie-Salmon Staging System (25) |
| International Staging System (ISS) | Stage III Serum β2-microglobulin ≥ 5.5 mg/L (other stages consider serum albumin levels as well) | Tumor Burden/ Stage | 2005 | Greipp et al. (26) |
| University of Arkansas for Medical Sciences (UAMS)17-gene model | High Risk Deregulated expression of 17 genes (1q32.1, 21q22.3, 1q21.2, 8q23.1, 10q23.31, 12q22, 1p36.21, 3p21.3, 7p14-p13, 1q22, 1q43, 1q31, 1p13.2, 1p22, 1p13.3, 2p22-p21, 6p21) | Cytogenetics | 2007 | Shaughnessy et al. (27) |
| Medical Research Council (MRC) Myeloma IX Trial | Adverse lesions defined as +1q21, del(17p13), del(13q14), or adverse IGH translocations t(4;14), t(14;16), or t(14;20) High Risk Presence of >1 adverse lesion Ultra-high Risk Presence of >1 adverse genetic lesions and ISS II or III | Combined Cytogenetics-ISS | 2012 | Boyd et al. (28) |
| mSMART | High Risk Genetic abnormalities on t(14;16), t(14;20), del(17p); GEP high risk signature | Cytogenetics | 2013 | Mikhael et al. (29) |
| International Myeloma Working Group (IMWG) | High Risk ISS II/III and t(4;14) or del(17p13) | Combined Cytogenetics-ISS | 2014 | Chng et al. (30) |
| Revised International Staging System (R-ISS) | Stage III ISS stage III (Serum β2-microglobulin 5.5 mg/L) and either: high risk CA by iFISH (presence of del(17p) and/or translocation t(4;14) and/or translocation t(14;16), or high lactate dehydrogenase (LDH) (serum LDH > the upper limit of normal) | Combined Cytogenetics-ISS | 2015 | Palumbo et al. (7) |
| mSMART 3.0 | High Risk Genetic abnormalities: t(4;14), t(14;16), t(14;20), del(17p), p53 mutation, +1q; RISS stage III; High plasma cell s-phase; high GEP risk signature | Combined Genetics-ISS | 2018 | Treatment Guidelines (31) |
CA, cytogenetic abnormality; GEP, gene expression profiling; iFISH, interphase fluorescence in situ hybridization; IGH, immunoglobulin heavy; ISS, International Staging System; LDH, lactate dehydrogenase; mSMART, Mayo stratification of myeloma and risk-adapted therapy; R-ISS, Revised International Staging System.