Mm Diagnostic Workup

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.