Smoldering Myeloma

Authored by Vincent Rajkumar, published on 2026-08-20 20:38:37.0

Treatment algorithm for smoldering myeloma. Incorporates the 2025 Daratumumab FDA approval for high risk smoldering myeloma. Active drugs in multiple myeloma reference.mSMART 4.0 Risk Stratification of active multiple myeloma.

  1. Potential New Myeloma or Smoldering Myeloma
    This entry node frames the initial diagnostic consideration and is supported by contemporary reviews and consensus discussions on SMM definitions, evaluation, and treatment paradigms.
    • Any Myeloma Defining Events?
      • CRAB, • ≥60% PC, • FLC ≥100, • MRI >1 focal
      • Treat as Myeloma
        Newly Diagnosed Myeloma treatment algorithm by Vincent Rajkumar, MD.
    • No Myeloma Defining Events (SMM)
      • Intermediate or Low Risk SMM
        • Observation
      • High Risk SMM (Median TTP ~2 years)
        • High Risk SMM or Evolving SMM
          • Daratumumab x 3 years*
            *Alternative is Len x 2 years; High risk by IMWG cytogenetics criteria, may consider MM therapy
        • Clinical Trials
tosprivacySmoldering multiple myeloma current treatment algorithmsHealthcare Unfiltered Episode 217: Smoldering Myeloma: The Epic DebateDaratumumab or Active Monitoring for High-Risk Smoldering Multiple MyelomaLenalidomide plus Dexamethasone for High-Risk Smoldering Multiple MyelomaRandomized Trial of Lenalidomide Versus Observation in Smoldering Multiple Myeloma