Mm Mrd Assessment

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name: mm-mrd-assessment
description: Decide when and how to assess minimal residual disease (MRD) in multiple myeloma — bone marrow MRD by next-generation flow (NGF) or sequencing (NGS), plus imaging MRD by PET-CT — and how to act on the result. Trigger when a clinician asks "how to assess MRD in myeloma", "MRD-negative complete response", "PET-CT for MRD", "is bone marrow MRD enough", "when to test for MRD", "next-generation flow for myeloma", or "myeloma sustained MRD negativity". Based on EHA-ESMO 2021.
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# Multiple Myeloma — MRD Assessment

Use this skill at the moment a patient achieves complete response (CR) or stringent CR, to decide *when*, *how*, and *what to do next*.

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## STEP 1 — Has the patient achieved at least conventional CR?

MRD testing is meaningful only after CR is reached.
- **No CR yet** → do not test MRD; continue current therapy or follow standard response criteria.
- **CR or sCR achieved** → proceed to Step 2.

(Exception: in non-secretory MM, CR is defined by BM and imaging — MRD testing follows the same path.)

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## STEP 2 — Test BONE MARROW MRD

Use one of:
- **Next-generation flow cytometry (NGF)** — preferred when NGS is not available
- **Next-generation sequencing (NGS)** — most sensitive

Threshold:
- **MRD-negative = absence of clonal plasma cells in <10⁻⁶ BM cells** (i.e. <1 clonal plasma cell per 1 000 000 BM cells).
- The 10⁻⁶ cut-off outperforms 10⁻⁵ for predicting both PFS and OS — request the higher-sensitivity assay where available.

If positive → patient is MRD-positive in marrow. Continue therapy/maintenance per standard pathway.
If negative → proceed to Step 3.

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## STEP 3 — Confirm IMAGING MRD with PET-CT

Why: 15–20% of patients who are MRD-negative in marrow have residual hypermetabolic disease on PET-CT. BM MRD alone misses extramedullary disease.

- Order **PET-CT** at the time of BM MRD-negative result.
- If PET-CT is **negative** → patient is "MRD-negative in BM and by imaging" — the deepest response category.
- If PET-CT is **positive** → patient has imaging-only residual disease; treat as MRD-positive for prognostic purposes.

PET-CT is the preferred modality for imaging MRD; whole-body MRI is not used for this purpose.

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## STEP 4 — Sustained MRD negativity (longitudinal monitoring)

A single MRD-negative result is not enough — durability matters.
- Repeat BM MRD assessment **annually** in patients on maintenance who are MRD-negative.
- Repeat **PET-CT every 12 months** in BM MRD-negative patients to confirm sustained imaging MRD negativity.
- Patients who *convert* from MRD-positive to MRD-negative during maintenance also have improved PFS — sequential assessment is informative.

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## STEP 5 — How to act on the MRD result

MRD currently informs **prognosis**, not yet routine treatment de-escalation.
- **Do NOT stop maintenance therapy based solely on MRD negativity** outside a clinical trial — this is under active investigation but not yet standard of care.
- MRD-positive in CR → consider whether the patient is in a high-risk subgroup; trial enrolment is appropriate.
- Use MRD status as a shared-decision-making tool with the patient about prognosis.

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## CLINICAL GUARDRAILS

- **MRD only counts if the assay reaches 10⁻⁶ sensitivity.** Lower-sensitivity flow (e.g. 4-colour) is not adequate.
- **Always pair BM with PET-CT.** A "marrow-only" MRD result misses ~1 in 5 patients with extramedullary disease.
- **MRD is not yet a treatment trigger** — do not de-escalate or stop therapy based on a single result outside a trial.
- **Reimbursement varies** — sustained MRD monitoring is supported by IMWG but not always funded; document clinical rationale.
- **Non-secretory and oligo-secretory MM** — MRD by BM + PET-CT is *especially* important here, as serum/urine markers are unreliable.

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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

Cross-references: IMWG consensus criteria for response and MRD (Kumar et al., *Lancet Oncol* 2016); Cavo et al. PET-CT consensus statement (*Lancet Oncol* 2017).