CHICAGO — Patients with smoldering myeloma with evolving change in monoclonal protein (eMP) and evolving change in hemoglobin (eHb) had an 80% or higher risk of progression to multiple myeloma within 2 years, regardless of the proportion of bone marrow plasma cells at the time of smoldering myeloma diagnosis, according to findings presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.1

“Smoldering multiple myeloma is characterized by an M-protein ≥3 g/dL and/or 10% to 60% clonal bone marrow plasma cells with no evidence of myeloma-defining event or amyloidosis,” said lead investigator Praful Kumar Ravi, MB, BChir, a physician in the department of internal medicine at Mayo Clinic in Rochester, MN. “Fourteen percent of patients with newly diagnosed multiple myeloma progressed from smoldering myeloma.”

Dr Ravi noted that the risk of progression to multiple myeloma is 10% per year for the first 5 years, 3% per year for the next 3 years, and 1% per year thereafter.

Continue Reading

Because there has been limited research on the impact of evolving changes in smoldering multiple myeloma biomarkers on risk of progression to multiple myeloma, Dr Ravi and colleagues sought to use such changes to identify a subgroup of patients with smoldering myeloma who are at ultra high-risk for progressing to multiple myeloma.

For the study, investigators identified 191 patients with smoldering myeloma who were treated at their institution from 1973 to 2014. Patients who received myeloma-specific therapy prior to progression or without adequate follow-up to evaluate evolving changes in biomarkers were excluded.

eMP was defined as a ≥10% increase in M-protein (M) and/or quantitative involved immunoglobulin (Ig) within 6 months of diagnosis (only if M ≥3) and/or ≥25% increase in M/Ig within 12 months, with a required minimum increase of 0.5 g/dL in M and/or 500 mg/dL in Ig. eHb was defined as ≥0.5 g/dL decrease within 12 months of diagnosis.

Results showed that 70.7% progressed to multiple myeloma and 31.9% progressed within 2 years of smoldering myeloma diagnosis. After a median follow-up of 10.4 years, the median time to progression was 3.9 years.

After adjusting for known factors of progression to multiple myeloma, researchers found that ≥20% bone marrow plasma cells at smoldering myeloma diagnosis (OR, 3.37; 95% CI, 1.30-8.77; P=.013), eMP (OR, 8.20; 95% CI, 3.19-21.05; P<.001) and eHb (OR, 5.86; 95% CI, 2.12-16.121; P=.001) independently predicted for progression within 2 years of smoldering myeloma diagnosis.

Investigators then developed a risk model comprising these variables, which showed that median time to progression was 12.3 years, 4.2 years, 2.8 years, and 1.0 years in patients with 0, 1, 2, and 3 risk factors, respectively (P<.001). Further, the 2-year risk of progression was 81.5% in patients with both eMP and eHb, and 90.5% in patients with all 3 risk factors.

RELATED: Molecular Profiles Differ Between High-risk Smoldering Myeloma, Newly Diagnosed Multiple Myeloma

“Smoldering multiple myeloma patients with eMP and eHB with or without bone marrow plasma cells ≥20% had a greater than 80% risk of progression to multiple myeloma within 2 years of diagnosis, and these patients comprise an ultra high-risk smoldering myeloma subgroup,” Dr Ravi explained.

Dr Ravi concluded that validation is required before these parameters can be added to diagnostic criteria for multiple myeloma or used to identify patients who could be candidates for early therapy.


  1. Ravi PK, Kumar S, Larsen JT, et al. Evolving changes in M-protein (M), quantitative involved immunoglobulin (Ig), and hemoglobin (Hb) to identify patients (pts) with ultra high-risk smoldering multiple myeloma (UHR-SMM). J Clin Oncol. 2016; 34 (suppl; abstr 8004).