Smoldering Multiple Myeloma

Table 1

Studies predicting risk of progression of SMM to symptomatic MM.

Author [year]	Included number and criteria	Risk factors	Outcome
Kyle et al. 2007 [15]	276 IMWG	Group 1 (BMPC ≥ 10% and M protein ≥ 30 g/L); group 2 (BMPC ≥ 10% and M protein < 30 g/L); group 3 (BMPC < 10% and M protein ≥ 30 g/L)	TTP: group 1: 2 y; group 2: 8 y; group 3: 19 y
Kastritis et al. 2013 [16]	96 IMWG	Risk factor 1: M protein ≥ 30 g/L; risk factor 2: extensive BM infiltration ≥ 60%; risk factor 3: FLC ratio ≥ 100; risk factor 4: abnormal MRI	TTP: with risk factor 1 was 2 y (versus 8 y without risk factor 1); with risk factor 2 was 15 m (versus 90 m without risk factor 2); with risk factor 3 was 18 m (versus 73 m without risk factor 3); with risk factor 4 was 15 m (versus not reached without risk factor 4).
Rajkumar et al. 2011 [17]	655 IMWG	BMPC ≥ 60%	2-y progression rate: 95%; TTP: 7 m
Pérez-Persona et al. 2007 [19]	93 IMWG	Group 1: neither aPCs/BMPC ≥ 95% nor immunoparesis; group 2: aPCs/BMPC ≥ 95% or immunoparesis; group 3: aPCs/BMPC ≥ 95% and immunoparesis	5-y progression rate: group 1: 4%; group 2: 46%; group 3: 72%
Pérez-Persona et al. 2010 [20]	61 IMWG	aPCs/BMPC ≥ 95%	3-y progression rate: for evolving SMM with aPCs/BMPC ≥ 95% was 46% (versus 8% with aPCs/BMPC < 95%); for nonevolving SMM with aPCs/BMPC ≥ 95% was 15% (versus no progressions with aPCs/BMPC < 95%)
Larsen et al. 2013 [21]	586 IMWG	FLC ratio ≥ 100	TTP: FLC ratio ≥ 100: 15 m; FLC ratio < 100: 55 m
Dispenzieri et al. 2008 [22]	273 IMWG	BMPC ≥ 10%; M protein ≥ 30 g/L; FLC ratio ≥ 8; low-risk: 1 risk factor; intermediate-risk: 2 risk factor; high-risk: 3 risk factor	5-y progression rate: low-risk: 25%; intermediate-risk: 51%; high-risk: 76%
Witzig et al. 1994 [23]	57 BMPC > 10% without CRAB	Abnormal PBPC (an increase in number or proliferative rate of PBPC)	TTP: with abnormal PBPC was 0.75 y (versus 2.5 y without abnormal PBPC)
Bianchi et al. 2013 [24]	91 IMWG	High PBPC (absolute PBPC > 5000 10^6/L and/or >5% cytoplasmic Ig positive PC per 100 PBMC)	2-y progression rate: with high PBPC was 71% (versus 25% without high PBPC); 3-y progression rate: with high PBPC was 86% (versus 34% without high PBPC)
Rosiñol et al.  2003 [25]	53 BMPC > 10%, M-protein > 30 g/L or light chain > 1 g, hemoglobin > 100 g/L, without CRAB	Evolving SMM (a progressive increase in M protein, a previously recognized MGUS and a significant higher proportion of IgA type)	TTP: with evolving SMM was 1.3 y (versus 3.9 y with nonevolving SMM)
Moulopoulos et al. 1995; [26]	38 BMPC > 10%, hemoglobin > 105 g/L, normocalcemia, M protein < 45 g/L, and no lytic bone lesion	Abnormal MRI	TTP: with abnormal MRI was 16 m (versus 43 m with normal MRI)
Hillengass et al. 2010 [27]	149 IMWG	Focal lesions > 1	2-y progression rate: 0 or 1 focal lesion: 20%; >1 focal lesion: 70%
Neben et al. 2013 [28]	248 IMWG	del (17p13), t(4;14), +1q21 and hyperdiploidy	TTP: with del (17p13) was 2.04 y (versus 5.62 y without del (17p13)); with t(4;14) was 2.91 y (versus 5.71 y without t(4;14)). 3-y progression rate: with +1q21 was 43% (versus 27% without +1q21); with hyperdiploidy was 35% (versus 29% without hyperdiploidy)
Rajkumar et al. 2013 [29]	351 IMWG	Low-risk: no detectable abnormalities; Standard-risk: t(11;14), MAF translocations, other/unknown IgH translocations, or monosomy 13/del (13q); Intermediate-risk: trisomies alone; High-risk: t(4;14)	TTP: High-risk: 28 m; Intermediate-risk: 34 m; Standard-risk: 55 m; Low-risk: not reached

PC: plasma cells; PBPC: peripheral blood plasma cells; PBMC: peripheral blood mononuclear cells; Ig: immunoglobulin; MRI: magnetic resonance imaging; FLC: serum free light chain; BMPC: bone marrow plasma cells; aPCs/BMPC: aberrant plasma cells within the bone marrow plasma cells; TTP: median time to progression; CRAB: hypercalcemia, renal failure, anemia, and bone lesions; IMWG: International Myeloma Working Group; m: month; y: year.