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Minimal residual disease
IMWG criteria for MRD in MM
- Requires a CR–negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in BM aspirates1
- MRD detected by NGF, NGS, or a validated equivalent technique with 10-5 as the minimum sensitivity level1
- To evaluate disease outside the bone marrow, imaging (PET, CT, MRI, or 18F-FDG PET) should also be performed1
Imaging plus MRD-negative1
- MRD-negativity in the BM 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-negative1
- MRD-negativity in BM (NGF or NGS, or both) and by imaging, confirmed minimum of 1 year apart
- Subsequent evaluations can be used to further specify the duration of negativity (e.g., MRD-negative at 5 years)
NGF
- Uses two 8-color combinations to identify myeloma cells and confirm clonality2,3
- This approach is widely accessible due to the use of 8-color instruments in many institutions1,2
- No baseline sample is required1,2
NGS1,3
- Uses specific primers to identify myeloma cells based on genetic sequences; this technique is highly sensitive
- A baseline sample to identify unique genetic sequences for individual patient is required
Depth of response as measured by remaining malignant cells4
Reproduced with permission of American Society of Hematology and HighWire Press. From Paiva B et al. New criteria for response assessment: role of minimal residual disease in multiple myeloma. Blood. 2015;125(20):3059-3068; permission conveyed through Copyright Clearance Center, Inc.4
BM, bone marrow; CR, complete response; CT, computerized tomography; DNA, deoxyribonucleic acid; FDG, fluorodeoxyglucose; IMWG, International Myeloma Working Group; MM, multiple myeloma; MRD, minimal residual disease; NGF, next generation flow; NGS, next generation sequencing; PET, positron emission tomography; PR, partial response; sCR, stringent complete response; SUV, maximum standardized uptake value; VGPR, very good partial response.
1. Kumar S, et al Lancet Oncol. 2016;17:e328-46. 2. Mailankody S, et al. Nat Rev Clin Oncol. 2015;12(5):286-295. 3. Martinez-Lopez J, et al. Blood. 2014;123(20):3073-3079. 4. Paiva B, et al. Blood. 2015;125(20):3059-3068.
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