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

• Published in: Blood advances 2018-06, Vol.2 (12), p.1470-1479
• Main Authors: Wu, Vernon, Moshier, Erin, Leng, Siyang, Barlogie, Bart, Cho, Hearn Jay, Jagannath, Sundar, Madduri, Deepu, Mazumdar, Madhu, Parekh, Samir, Chari, Ajai
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers; Bone Marrow - pathology; Disease Progression; Hemoglobins - metabolism; Humans; Immunoglobulin Light Chains - blood; Lymphoid Neoplasia; Middle Aged; Models, Theoretical; Myeloma Proteins - metabolism; Plasma Cells - pathology; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Smoldering Multiple Myeloma - diagnosis; Young Adult
• ISSN: 2473-9529; 2473-9537
• 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. •FLCr ≥100 and BMPC ≥60% identify high-risk SMM, although with more modest median TTP and 2-year PD than previously published.•Baseline immunoparesis, eMP, eHb, and edFLC can help identify an ultra-high-risk SMM cohort. [Display omitted]