| 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. |
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.
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
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
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
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.
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)
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.
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.
