Prognostic factors for progression of SMM to active MM
| Reference . | n . | % BMPC, (M protein, g/L), [other criteria] . | Risk factors . | Median TTP and OS . |
|---|---|---|---|---|
| Wisloff et al, 199120 | 71 | ≥10, (*or IgA > 15, IgG > 30, Bence Jones proteinuria > 1 g/24 h) | Lytic bone lesions; BMPCs > 20% | TTP 26 mo; OS 45 mo; no risk: TTP 39 mo; either risk: TTP 10 mo |
| Dimopoulos et al, 199324 | 95 | >15, (*and serum M protein < 45 g/L), [any lytic bone lesion was exclusionary; > hemoglobin 10.5 g/dL] | Protein risk: M protein > 30 g/L or proteinuria > 50 mg/24 h; low (n = 27): no factor; intermediate (n = 43): either protein characteristic; high (n = 25): lytic bone lesions and/or both protein risk characteristics | TTP: 26 mo; low: 61 mo; intermediate: 25 mo; high: 10 mo; OS from SMM (from treatment): low: 89 mo (35 mo); intermediate: 92 mo (31 mo); high: 57 mo (41 mo) |
| Witzig et al, 199428 | 57 | >10, (not stated), [no CRAB] | Circulating cells by PBLI (n = 14) | TTP: circulating: 9 mo; no circulating: 30 mo |
| Facon et al, 199522 | 91 | >15%, (*and DSS I) | Hemoglobin < 12 g/dL; BMPC > 20%; M protein > 30 g/L (IgG) or > 25 g/L (IgA); 0 factor (n = 38); 1 factor (n = 35); >1 factor (n = 18) | TTP: 48 mo: 0: > 50 mo; 1: 26 mo; >1 factor: 6 mo; OS from SMM (from treatment): 0: > 70 m (33 mo); 1: 50 mo (31 mo); >1: 38 mo (32 mo) |
| Moulopolous et al, 199533 | 38 | >10, (or M-spike > 25-45 g/L or Bence Jones > 150 mg/d), [hemoglobin > 10.5 g/dL; no lytic bone lesions] | Abnormal MRI | TTP: normal MRI: 43 mo; abnormal MRI: 16 mo; variegated: 22 mo; diffuse: 16 mo; focal: 6 mo |
| Weber et al, 199723 | 101 | See Moupolous et al, 1995 | M protein > 30 g/L; IgA M protein; proteinuria > 50 mg/24 h; low (n = 16): 0; intermediate (n = 65): 1; high (n = 20): 2 or more | TTP: low: 95 mo; intermediate: 39 mo; high: 17 mo; OS from dexamethasone (from treatment): low: 89 mo (26 mo); intermediate: 87 mo (34 mo); high: 51 mo (32 mo) |
| Kyle et al, 200721 | 276 | IMWG | M protein ≥ 30; BMPC ≥ 10%; group A: M protein only (n = 27); group B: BMPC only (n = 143); group C: both (n = 106) | 2-y TTP (5-y TTP): A: 6% (15%); B: 22% (43%); C: 45% (69%) |
| Perez-Persona et al, 200731 | IMWG | 95% aberrant BMPC (absence of CD19 and/or CD45 expression, overexpression of CD56, or weak expression of CD38); immunoparesis of the uninvolved immunoglobulins: neither (n = 28), either (n = 39), both (n = 39) | Median TTP (5-y TTP): neither: NR (4%); either: 73 mo (46%); both: 23 mo (72%) | |
| Dispenzieri et al, 200825 | 273 | IMWG | M protein ≥ 30; BMPC ≥ 10%; involved FLC/uninvolved; FLC ≥ 8; 1 high (n = 81); 2 high (n = 114); 3 high (n = 78) | 2-y TTP (5-y TTP): 1: 12% (25%); 2: 27% (51%); 3: 52% (76%) |
| Hillengass et al, 201034 | 149 | IMWG | Whole-body MRI: low (n = 126): no or 1 focal lesion; high (n = 23): > 1 focal lesion | Median (2-y TTP): low: not reached (20%); high: 13 mo (70%) |
| Rajkumar et al, 201162 | 655 | IMWG | BMPCs ≥ 60% (n = 21)* | Median TTP (2-y TTP): BMPC ≥ 60%: 7 mo (95%) |
| Larsen et al, 201326 | 586 | IMWG | Involved FLC/uninvolved FLC < 100 (n = 496); involved FLC/uninvolved FLC ≥ 100 (n = 90) | Median (2-y TTP; 5-y TTP); low: NR (28%; 53); high: 15 mo (79%; 94%) |
| Bianchi et al, 2013 29 | 91 | IMWG | High: slide based > 5 × 106/L or > 5% PC/100 cIg MNC; low (n = 77); high (n = 14) | Median (2-y TTP): low: 57 mo (24%); high: 12 mo (71%); OS from SMM (from treatment): low: 148 mo (66 mo); high: 49 mo (31 mo) |
| Rago et al, 201359 | 397 | IMWG | Hemoglobin ≤ 12.5; M protein ≥ 2.5; BMPC ≥ 60 (2.5% of patients) | 10-y TTP: 45%; BMPC ≥ 60% had × 5.6 risk of progression |
| Madan et al, 201030 | 175 | IMWG | PCLI < 1%; PCLI ≥ 1% | 2-y TTP (5-y TTP): low: 40% (60%); high: 60% (68%) |
| Rajkumar et al, 201338 | 351 | IMWG | FISH: low: (n = 53), normal or insufficient; standard: (n = 106), t(11;14), maf translocations, other/unknown translocations, or deletion 13/13q; intermediate: (n = 148), trisomies alone; high: (n = 44), t(4;14) or deletion 17p | TTP: low: not reached; standard: 54 mo; intermediate: 34 mo; high: 24 mo; OS from SMM (from treatment): low, 135 mo (60 mo); standard, 147 mo (77 mo); intermediate, 135 mo (86 mo); high risk, 105 mo (60 mo) |
| Kastritis et al, 201327 | 96 | IMWG | Risk factors: involved FLC/uninvolved FLC ≥ 100; BM ≥ 60% | Median TTP: no risk factor: 73 mo; 1 risk factor: 18 mo; both risk factors 8 mo |
| Neben et al, 201239 | 246 | IMWG | High-risk FISHs: t(4:14), deletion 17p or +1q21; high tumor burden: M protein ≥ 20 g/L; FISH and tumor burden: both low risk (n = 81); FISH high risk, tumor low risk (n = 44); FISH low risk, tumor high risk (n = 76); both high risk (n = 44) | 3-y TTP: both low risk: 8%; FISH high risk only: 30%; tumor high risk only: 40%; both high risk: 59% |
| Reference . | n . | % BMPC, (M protein, g/L), [other criteria] . | Risk factors . | Median TTP and OS . |
|---|---|---|---|---|
| Wisloff et al, 199120 | 71 | ≥10, (*or IgA > 15, IgG > 30, Bence Jones proteinuria > 1 g/24 h) | Lytic bone lesions; BMPCs > 20% | TTP 26 mo; OS 45 mo; no risk: TTP 39 mo; either risk: TTP 10 mo |
| Dimopoulos et al, 199324 | 95 | >15, (*and serum M protein < 45 g/L), [any lytic bone lesion was exclusionary; > hemoglobin 10.5 g/dL] | Protein risk: M protein > 30 g/L or proteinuria > 50 mg/24 h; low (n = 27): no factor; intermediate (n = 43): either protein characteristic; high (n = 25): lytic bone lesions and/or both protein risk characteristics | TTP: 26 mo; low: 61 mo; intermediate: 25 mo; high: 10 mo; OS from SMM (from treatment): low: 89 mo (35 mo); intermediate: 92 mo (31 mo); high: 57 mo (41 mo) |
| Witzig et al, 199428 | 57 | >10, (not stated), [no CRAB] | Circulating cells by PBLI (n = 14) | TTP: circulating: 9 mo; no circulating: 30 mo |
| Facon et al, 199522 | 91 | >15%, (*and DSS I) | Hemoglobin < 12 g/dL; BMPC > 20%; M protein > 30 g/L (IgG) or > 25 g/L (IgA); 0 factor (n = 38); 1 factor (n = 35); >1 factor (n = 18) | TTP: 48 mo: 0: > 50 mo; 1: 26 mo; >1 factor: 6 mo; OS from SMM (from treatment): 0: > 70 m (33 mo); 1: 50 mo (31 mo); >1: 38 mo (32 mo) |
| Moulopolous et al, 199533 | 38 | >10, (or M-spike > 25-45 g/L or Bence Jones > 150 mg/d), [hemoglobin > 10.5 g/dL; no lytic bone lesions] | Abnormal MRI | TTP: normal MRI: 43 mo; abnormal MRI: 16 mo; variegated: 22 mo; diffuse: 16 mo; focal: 6 mo |
| Weber et al, 199723 | 101 | See Moupolous et al, 1995 | M protein > 30 g/L; IgA M protein; proteinuria > 50 mg/24 h; low (n = 16): 0; intermediate (n = 65): 1; high (n = 20): 2 or more | TTP: low: 95 mo; intermediate: 39 mo; high: 17 mo; OS from dexamethasone (from treatment): low: 89 mo (26 mo); intermediate: 87 mo (34 mo); high: 51 mo (32 mo) |
| Kyle et al, 200721 | 276 | IMWG | M protein ≥ 30; BMPC ≥ 10%; group A: M protein only (n = 27); group B: BMPC only (n = 143); group C: both (n = 106) | 2-y TTP (5-y TTP): A: 6% (15%); B: 22% (43%); C: 45% (69%) |
| Perez-Persona et al, 200731 | IMWG | 95% aberrant BMPC (absence of CD19 and/or CD45 expression, overexpression of CD56, or weak expression of CD38); immunoparesis of the uninvolved immunoglobulins: neither (n = 28), either (n = 39), both (n = 39) | Median TTP (5-y TTP): neither: NR (4%); either: 73 mo (46%); both: 23 mo (72%) | |
| Dispenzieri et al, 200825 | 273 | IMWG | M protein ≥ 30; BMPC ≥ 10%; involved FLC/uninvolved; FLC ≥ 8; 1 high (n = 81); 2 high (n = 114); 3 high (n = 78) | 2-y TTP (5-y TTP): 1: 12% (25%); 2: 27% (51%); 3: 52% (76%) |
| Hillengass et al, 201034 | 149 | IMWG | Whole-body MRI: low (n = 126): no or 1 focal lesion; high (n = 23): > 1 focal lesion | Median (2-y TTP): low: not reached (20%); high: 13 mo (70%) |
| Rajkumar et al, 201162 | 655 | IMWG | BMPCs ≥ 60% (n = 21)* | Median TTP (2-y TTP): BMPC ≥ 60%: 7 mo (95%) |
| Larsen et al, 201326 | 586 | IMWG | Involved FLC/uninvolved FLC < 100 (n = 496); involved FLC/uninvolved FLC ≥ 100 (n = 90) | Median (2-y TTP; 5-y TTP); low: NR (28%; 53); high: 15 mo (79%; 94%) |
| Bianchi et al, 2013 29 | 91 | IMWG | High: slide based > 5 × 106/L or > 5% PC/100 cIg MNC; low (n = 77); high (n = 14) | Median (2-y TTP): low: 57 mo (24%); high: 12 mo (71%); OS from SMM (from treatment): low: 148 mo (66 mo); high: 49 mo (31 mo) |
| Rago et al, 201359 | 397 | IMWG | Hemoglobin ≤ 12.5; M protein ≥ 2.5; BMPC ≥ 60 (2.5% of patients) | 10-y TTP: 45%; BMPC ≥ 60% had × 5.6 risk of progression |
| Madan et al, 201030 | 175 | IMWG | PCLI < 1%; PCLI ≥ 1% | 2-y TTP (5-y TTP): low: 40% (60%); high: 60% (68%) |
| Rajkumar et al, 201338 | 351 | IMWG | FISH: low: (n = 53), normal or insufficient; standard: (n = 106), t(11;14), maf translocations, other/unknown translocations, or deletion 13/13q; intermediate: (n = 148), trisomies alone; high: (n = 44), t(4;14) or deletion 17p | TTP: low: not reached; standard: 54 mo; intermediate: 34 mo; high: 24 mo; OS from SMM (from treatment): low, 135 mo (60 mo); standard, 147 mo (77 mo); intermediate, 135 mo (86 mo); high risk, 105 mo (60 mo) |
| Kastritis et al, 201327 | 96 | IMWG | Risk factors: involved FLC/uninvolved FLC ≥ 100; BM ≥ 60% | Median TTP: no risk factor: 73 mo; 1 risk factor: 18 mo; both risk factors 8 mo |
| Neben et al, 201239 | 246 | IMWG | High-risk FISHs: t(4:14), deletion 17p or +1q21; high tumor burden: M protein ≥ 20 g/L; FISH and tumor burden: both low risk (n = 81); FISH high risk, tumor low risk (n = 44); FISH low risk, tumor high risk (n = 76); both high risk (n = 44) | 3-y TTP: both low risk: 8%; FISH high risk only: 30%; tumor high risk only: 40%; both high risk: 59% |
cIg, cytoplasmic immunoglobulin; MNC, mononuclear cells; NR, no response; PBLI, peripheral blood labeling index; PC, plasma cells; and PCLI, plasma cell labeling index.
The estimate of bone marrow plasmacytosis was according to the methods of Rajkumar et al35 (ie, using the highest estimate of plasma cells from the aspirate or the bone marrow).