dromlakhani 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.
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.)
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.
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.
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.
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.
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.
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).