- Article
- Source: Campus Sanofi
- Jun 4, 2025
About MRD
MRD: Lingering Posttreatment Malignant Cells That May Eventually Cause Relapse
- MRD describes the low level of malignant cells that persist in the bone marrow after treatment but cannot be detected with conventional outcome measures and which eventually lead to relapse1,2
- A patient who is MRD negative has achieved clinical remission with the absence of aberrant clonal cells by NGF or NGS per at least 100,000 nucleated cells2
- Even patients in CR may remain MRD+, if residual malignant cells are detected on a test sample. Studies have shown that patients in CR with persistent MRD have outcomes on par with patients in PR3-6
- Current IMWG criteria for MRD- defines the threshold as a minimum sensitivity of 10-5, although as testing has improved it has become increasingly common to establish MRD- at a threshold of 10-6 2,7
Defining MRD per IMWG response criteria2
Highest ← Detectable tumour burden in blood and bone marrow → Lowest
SD: Stable disease/no change
Not meeting criteria for CR, VGPR, PR, minimal response, or progressive disease
PR: Partial Response
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A ≥ 50% reduction of serum M-protein and reduction in 24h urinary M-protein by ≥ 90% or to <200 mg/24 h
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If serum and urine M-protein are unmeasurable, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria
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If serum and urine M-protein and serum-free light assay are unmeasurable, a ≥ 50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥ %30
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In addition to the above listed criteria, if present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required
VGPR: Very Good Partial Response
Serum and urine M-protein detectable by immunoflixation but not on electrophoresis or ≥ 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h
CR: Complete Response
Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and < 5% plasma cells in bone marrow aspirates
sCR: Stringent Complete Response
CR plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry
MRD-a: Minimal Residual Disease Negativity
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Flow MRD-negative: Absence of phenotypically aberrant clonal plasma cells by NGF on bone marrow aspirates using the EuroFlow standard operation procedure for MRD detection in multiple myeloma (or validated equivalent method) with a minimum sensitivity of 1 in 105 nucleated cells or higher
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Sequencing MRD-negative: Absence of clonal plasma cells by NGS on bone marrow aspirate in which presence of a clone is defined as <2 identical sequencing reads obtained after DNA sequencing of bone marrow aspirates using the LymphoSIGHT platform (or validated equivalent method) with a minimum sensitivity of 1 in 105 nucleated cells or higher
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Imaging plus MRD-negative: MRD negativity as defined by NGF or NGS plus disappearance of every area of increased tracer uptake found at baseline or a preceding PET/CT or decrease to less mediastinal blood pool SUV or decrease to less than that of surrounding normal tissue
Sustained MRD-b: Sustained Minimal Residual Disease Negativity
MRD negativity in the marrow (NGF or NGS, of both) and by imaging as defined on the previous slide, confirmed minimum of 1 year apart. Subsequent evaluations can be used to further specify the duration of negativity (eg, MRD-negative at 5 years)
aRequires a CR.
bSustained MRD negativity when reported should also annotate the method used (eg, sustained flow MRD-negative, sustained sequencing MRD-negative).
CR=complete response; FLC=free light chain; IMWG=International Myeloma Working Group; M-protein=myeloma protein; MRD=minimal residual disease; MRD-=minimal residual disease negativity; MRD+=minimal residual disease positivity; NGF=next-generation flow; NGS=next-generation sequencing; PET/CT=positron emission tomography–computed tomography; PR=partial response; sCR=stringent complete response; SD=stable disease; SUV=standardised uptake value; VGPR=very good partial response.
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MAT-AE-2200366-V2-Oct-23