| Response criteria* |
IMWG MRD criteria (requires a complete response as defined below) |
Sustained MRD-negative | MRD negativity in the marrow (NGF or NGS, or both) and by imaging as defined below, confirmed minimum of 1 year apart. Subsequent evaluations can be used to further specify the duration of negativity (eg, MRD-negative at 5 years).¶ |
Flow MRD-negative | Absence of phenotypically aberrant clonal plasma cells by NGFΔ 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. |
Sequencing MRD-negative | Absence of clonal plasma cells by NGS on bone marrow aspirate in which presence of a clone is defined as less than two 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. |
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 than the mediastinal blood pool SUV or decrease to less than that of surrounding normal tissue.§ |
Standard IMWG response criteria¥ |
Stringent complete response | Complete response as defined below plus normal FLC ratio‡ and absence of clonal cells in bone marrow biopsy by immunohistochemistry (κ/λ ratio ≤4:1 or ≥1:2 for κ and λ patients, respectively, after counting ≥100 plasma cells).† |
Complete response | Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow aspirates. |
Very good partial response | Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours. |
Partial response | ≥50% reduction of serum M-protein plus reduction in 24 hour urinary M-protein by ≥90% or to <200 mg per 24 hours. If the 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. If serum and urine M-protein are unmeasurable, and serum-free light assay is also unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma-cell percentage was ≥30%. In addition to these criteria, if present at baseline, a ≥50% reduction in the size (SPD)** of soft tissue plasmacytomas is also required. |
Minimal response | ≥25% but ≤49% reduction of serum M-protein and reduction in 24-hour urine M-protein by 50 to 89%. In addition to the above listed criteria, if present at baseline, a ≥50% reduction in the size (SPD)** of soft tissue plasmacytomas is also required. |
Stable disease | Not recommended for use as an indicator of response; stability of disease is best described by providing the time-to-progression estimates. Not meeting criteria for complete response, very good partial response, partial response, minimal response, or progressive disease. |
Progressive disease¶¶,ΔΔ | Any one or more of the following criteria: - Increase of 25% from lowest confirmed response value in one or more of the following criteria:
- Serum M-protein (absolute increase must be ≥0.5 g/dL);
- Serum M-protein increase ≥1 g/dL, if the lowest M component was ≥5 g/dL;
- Urine M-protein (absolute increase must be ≥200 mg/24 hours);
- In patients without measurable serum and urine M-protein levels, the difference between involved and uninvolved FLC levels (absolute increase must be >10 mg/dL);
- In patients without measurable serum and urine M-protein levels and without measurable involved FLC levels, bone marrow plasma-cell percentage irrespective of baseline status (absolute increase must be ≥10%);
- Appearance of a new lesion(s), ≥50% increase from nadir in SPD** of >1 lesion, or ≥50% increase in the longest diameter of a previous lesion >1 cm in short axis;
- ≥50% increase in circulating plasma cells (minimum of 200 cells per microL) if this is the only measure of disease.
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Clinical relapse | Clinical relapse requires one or more of the following criteria: - Direct indicators of increasing disease and/or end organ dysfunction (CRAB features) related to the underlying clonal plasma-cell proliferative disorder. It is not used in calculation of time to progression or progression-free survival but is listed as something that can be reported optionally or for use in clinical practice;
- Development of new soft tissue plasmacytomas or bone lesions (osteoporotic fractures do not constitute progression);
- Definite increase in the size of existing plasmacytomas or bone lesions. A definite increase is defined as a 50% (and ≥1 cm) increase as measured serially by the SPD** of the measurable lesion;
- Hypercalcemia (>11 mg/dL);
- Decrease in hemoglobin of ≥2 g/dL not related to therapy or other non-myeloma-related conditions;
- Rise in serum creatinine by 2 mg/dL or more from the start of the therapy and attributable to myeloma;
- Hyperviscosity related to serum paraprotein.
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Relapse from complete response (to be used only if the end point is disease-free survival) | Any one or more of the following criteria: - Reappearance of serum or urine M-protein by immunofixation or electrophoresis;
- Development of ≥5% plasma cells in the bone marrow;
- Appearance of any other sign of progression (ie, new plasmacytoma, lytic bone lesion, or hypercalcemia [refer to 'clinical relapse' above]).
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Relapse from MRD negative (to be used only if the end point is disease-free survival) | Any one or more of the following criteria: - Loss of MRD negative state (evidence of clonal plasma cells on NGF or NGS, or positive imaging study for recurrence of myeloma);
- Reappearance of serum or urine M-protein by immunofixation or electrophoresis;
- Development of ≥5% clonal plasma cells in the bone marrow;
- Appearance of any other sign of progression (ie, new plasmacytoma, lytic bone lesion, or hypercalcemia).
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