Mm Diagnostic Workup

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name: mm-diagnostic-workup
description: Order the correct work-up for a patient with multiple myeloma (MM) at four clinical timepoints — diagnosis, response assessment, follow-up, and relapse — using the EHA-ESMO 2021 framework. Trigger when a clinician asks "what tests to order for myeloma", "MM diagnosis workup", "myeloma follow-up tests", "tests at relapse for myeloma", "what to do for newly diagnosed multiple myeloma", or "investigations for plasma cell dyscrasia". Covers blood, urine, bone marrow, and imaging.
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# Multiple Myeloma — Diagnostic & Follow-up Workup

Use this skill to order the right tests at the right time. Walk through the four timepoints below and pick only the column that matches the patient.

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## STEP 1 — Identify the timepoint

Pick one:
- **Diagnosis** — newly suspected or newly confirmed MM, before any therapy
- **Response assessment** — at end of induction, after ASCT, or to confirm CR/sCR/MRD
- **Follow-up** — patient in remission on maintenance or watch-and-wait
- **Relapse** — biochemical or clinical progression suspected

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## STEP 2 — Order the tests for that timepoint

### A. AT DIAGNOSIS (obligatory unless stated)

**Blood**
- Full blood count + blood smear
- Serum protein electrophoresis + immunofixation (IF)
- Serum free light chains (sFLC)
- Serum immunoglobulin levels
- Renal function, liver function, calcium, LDH, albumin, β2-microglobulin
- Flow cytometry — *optional*

**Urine**
- 24-hour urine collection (proteinuria + light-chain proteinuria)
- Urine electrophoresis + IF

**Bone marrow**
- Cytology + biopsy (confirm plasmacytosis + monoclonality)
- NGF or NGS for clonal plasma cells — *for clinical trials only*
- Cytogenetics — karyotype + FISH for **del17p, t(4;14), t(14;16), 1q gain/amp, t(11;14)**
- GEP / NGS — *advanced, trials only*

**Imaging**
- Whole-body low-dose CT (WBLD-CT) — obligatory
- PET-CT — optional (may replace WBLD-CT if available)
- Whole-body MRI — obligatory if WBLD-CT negative and no PET-CT

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### B. AT RESPONSE ASSESSMENT

**Blood**
- FBC, electrophoresis (IF if confirming CR), sFLC (obligatory to confirm sCR), Ig levels, renal/liver function, calcium, LDH
- β2-microglobulin and flow cytometry — *not required*

**Urine**
- 24-h sample + electrophoresis (IF for CR confirmation)

**Bone marrow**
- Cytology + biopsy if confirming CR or in non-secretory MM
- **NGF or NGS** — obligatory to confirm MRD negativity in CR/sCR
- Cytogenetics, GEP/NGS — not required (trials only)

**Imaging**
- WBLD-CT — not required
- **PET-CT — obligatory to confirm imaging MRD**
- Whole-body MRI — not required

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### C. AT FOLLOW-UP

Carry out monthly or every 3 months:
- FBC, serum + urine electrophoresis, sFLC, creatinine, calcium

Periodic:
- Ig levels, IF (for CR patients)
- PET-CT every 12 months in BM MRD-negative patients (to confirm extramedullary MRD negativity)
- Whole-body MRI / WBLD-CT only if symptomatic (or CT of symptomatic area)

Not needed routinely: BM cytology, cytogenetics, GEP.

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### D. AT RELAPSE

**Blood + urine** — repeat full diagnostic panel (as in Step 2A).

**Bone marrow**
- Cytology + biopsy — obligatory
- **FISH** — obligatory for del17p, 1q gain/amp, t(11;14) (these drive treatment selection — e.g. t(11;14) → venetoclax-based therapy if available)

**Imaging**
- WBLD-CT — obligatory
- PET-CT or whole-body MRI — optional (use if symptomatic or to detect extramedullary disease)

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## STEP 3 — Clinical guardrails

- **sFLC at follow-up is non-negotiable.** It is the only way to detect light-chain escape early. Don't skip it.
- **Always FISH at relapse**, even if cytogenetics were normal at diagnosis — clones evolve, and del17p / 1q gain at relapse changes therapy.
- **Imaging MRD ≠ BM MRD.** Roughly 15–20% of patients who are MRD-negative in marrow have residual hypermetabolic disease on PET-CT. Confirm both.
- **Non-secretory MM** — serum/urine electrophoresis won't track disease. Rely on sFLC, BM, and imaging.
- **Don't repeat WBLD-CT during routine follow-up** if asymptomatic — only if bone pain or other red flag.

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## SOURCE

Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. *Annals of Oncology* 2021;32(3):309–322. DOI: 10.1016/j.annonc.2020.11.014

Adapted from Table 1 of the published guideline.