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Multiple myeloma and MGUS
Myeloma = 10% or more clonal plasma cells in the marrow with organ damage (CRAB: high calcium, kidney, anaemia, bone) or a SLiM marker; without organ damage it is MGUS or smouldering myeloma — observation, not treatment.
Why it matters in the exam
The typical question presents an older adult with bone pain (mainly back), anaemia, hypercalcaemia and kidney failure, sometimes with a very high ESR, a high total protein with low albumin and "rouleaux" on the film. The work-up: serum protein electrophoresis plus immunofixation, free light chains in serum and a bone marrow examination; imaging by whole-body low-dose CT. A well-known distractor: a bone scan is often normal, because the lesions are "purely osteolytic" with no bone-forming activity, and the ALP is normal.
Three states must be separated: MGUS — M protein below 3 g/dL, plasma cells below 10%, no organ damage; a progression risk of about 1% a year, so observation only. Smouldering myeloma — M protein of 3 g/dL or more or plasma cells of 10%–60% without organ damage. Active myeloma — CRAB (calcium above 11 mg/dL, creatinine above 2 mg/dL, Hb below 10 g/dL, bone lesions) or SLiM (plasma cells 60% or more, light-chain ratio 100 or more, more than one focal lesion on MRI). Treatment for a fit patient: bortezomib, lenalidomide and dexamethasone (sometimes with daratumumab), followed by autologous transplant, together with a bisphosphonate or denosumab, thrombosis prevention with lenalidomide and zoster prevention with bortezomib.
Key points
- Myeloma: plasma cells 10% or more + CRAB or SLiM.
- MGUS: M protein below 3 g/dL, plasma cells below 10%, no CRAB — observe.
- CRAB: calcium above 11, creatinine above 2, Hb below 10, bone lesions.
- Imaging by low-dose CT, not a bone scan.
- Treatment: bortezomib, lenalidomide, dexamethasone, autologous transplant and a bisphosphonate.
Summary table
| State | Definition | Action | Exam note |
|---|---|---|---|
| MGUS | M protein below 3 g/dL, plasma cells below 10%, no CRAB | Observation | Risk about 1% a year |
| Smouldering myeloma | M protein 3 g/dL or more or plasma cells 10%–60%, no CRAB | Close observation | Not routinely treated |
| Active myeloma — CRAB | Calcium above 11 mg/dL, creatinine above 2 mg/dL, Hb below 10 g/dL, bone lesions | Treat | Plasma cells 10% or more |
| Active myeloma — SLiM | Plasma cells 60% or more, light-chain ratio 100 or more, more than one MRI lesion | Treat even without CRAB | High-risk markers |
| Work-up | Electrophoresis, immunofixation, light chains, marrow | Whole-body low-dose CT | Not a bone scan |
| Treatment if fit | Bortezomib + lenalidomide + dexamethasone ± daratumumab | Autologous transplant | Bisphosphonate, thrombosis and zoster prevention |
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Sources
- International Myeloma Working Group (IMWG) updated criteria for the diagnosis of multiple myeloma, 2014 — CRAB and SLiM criteria; MGUS and smouldering myeloma
- Harrison's Principles of Internal Medicine, 21st edition (2022) — Plasma Cell Disorders
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-02. The text may contain errors; when in doubt, check the source.