Risk stratification of smoldering multiple myeloma: predictive value of free light chains and group-based trajectory modeling

Blood Adv. 2018 Jun 26;2(12):1470-1479. doi: 10.1182/bloodadvances.2018016998.


We investigated the predictive role for serum free light chain ratio (FLCr) ≥100, bone marrow plasma cell (BMPC) ≥60%, and evolving biomarkers through group-based trajectory modeling (GBTM) as high-risk defining events in 273 smoldering multiple myeloma (SMM) patients with a median follow-up of 74 months. FLCr ≥100 was confirmed as a marker for high-risk progression with a median time to progression (TTP) of 40 months with a 44% risk of progression of disease (PD) at 2 years; however, 44% of FLCr ≥100 also did not progress during follow-up. For patients with BMPC ≥60% by core biopsy, the median TTP was 31 months with a 2-year PD of 41%. GBTM established high-risk trajectories for evolving hemoglobin (eHb; characterized as a 1.57 g/dL decrease in hemoglobin), evolving m-protein (eMP; 64% increase in m-protein), and evolving differences in FLC (edFLC; 169% increase in dFLC) within 1 year of diagnosis associated with a decreased median TTP and an increased 2 year rate of PD. Of all the variables examined, we identify a model where immunoparesis, eHb, eMP, and edFLC were significant predictors for ultra-high-risk progression with a median TTP of only 13 months with 3 or more variables present. Our results not only confirm a more modest 2 year PD associated with FLCr ≥100 and BMPC ≥60 but also suggest that eHb, eMP, and edFLC may help identify an ultra-high-risk SMM group.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Bone Marrow / pathology
  • Disease Progression
  • Hemoglobins / metabolism
  • Humans
  • Immunoglobulin Light Chains / blood*
  • Middle Aged
  • Models, Theoretical*
  • Myeloma Proteins / metabolism
  • Plasma Cells / pathology*
  • Predictive Value of Tests
  • Retrospective Studies
  • Risk Assessment
  • Smoldering Multiple Myeloma / diagnosis*
  • Young Adult


  • Biomarkers
  • Hemoglobins
  • Immunoglobulin Light Chains
  • Myeloma Proteins
  • multiple myeloma M-proteins