Table 1.

Characteristics of available MRD assays

End pointAssayDisadvantageTarget group(s)
CR/sCR Standard technology Less sensitive NDMM elderly/frail 
Benchmark in clinical trial RRMM 
Widely applicable  
Evidence based  
No extra costs  
No need for central laboratory  
MRD by MFC Represents immunophenotypic response Requires processing within 48 h Transplant-eligible NDMM 
Sensitivity ≥10−4 Requires ≥5 × 106 cells Clinical trials 
Standard Euroflow protocol Cost of assay  
Automated analysis Less sensitive than NGS  
Available in many centers   
MRD by qPCR Represents molecular response Labor intensive Transplant-eligible NDMM 
Sensitivity ≥10−5 Requires ≥106 cells Clinical trials 
Standardized in ALL and other diseases Applicable in ≤70% of patients  
Widely available Requires baseline sample  
MRD by VDJ NGS Sensitivity ≥10−5 Labor intensive Transplant-eligible NDMM 
Commercial product by 1-2 companies Requires ≥106 cells Clinical trials 
 Applicable in ≤90% of patients  
 Requires bioinformatics  
 Requires baseline sample  
(MRD+)PET-CT Evaluation of extramedullary disease Standard not yet defined as in lymphomas All 
Widely available 
MRD by CTCs/RNA/DNA Assay in blood Requires single-cell NGS All 
No sampling error Not widely available 
Represents whole-body tumor mass Not standardized 
End pointAssayDisadvantageTarget group(s)
CR/sCR Standard technology Less sensitive NDMM elderly/frail 
Benchmark in clinical trial RRMM 
Widely applicable  
Evidence based  
No extra costs  
No need for central laboratory  
MRD by MFC Represents immunophenotypic response Requires processing within 48 h Transplant-eligible NDMM 
Sensitivity ≥10−4 Requires ≥5 × 106 cells Clinical trials 
Standard Euroflow protocol Cost of assay  
Automated analysis Less sensitive than NGS  
Available in many centers   
MRD by qPCR Represents molecular response Labor intensive Transplant-eligible NDMM 
Sensitivity ≥10−5 Requires ≥106 cells Clinical trials 
Standardized in ALL and other diseases Applicable in ≤70% of patients  
Widely available Requires baseline sample  
MRD by VDJ NGS Sensitivity ≥10−5 Labor intensive Transplant-eligible NDMM 
Commercial product by 1-2 companies Requires ≥106 cells Clinical trials 
 Applicable in ≤90% of patients  
 Requires bioinformatics  
 Requires baseline sample  
(MRD+)PET-CT Evaluation of extramedullary disease Standard not yet defined as in lymphomas All 
Widely available 
MRD by CTCs/RNA/DNA Assay in blood Requires single-cell NGS All 
No sampling error Not widely available 
Represents whole-body tumor mass Not standardized 

ALL, acute lymphoblastic leukemia; CTCs, circulating tumor cells; MFC, multiparameter flow cytometry; NDMM, newly diagnosed MM; NGS, next-generation sequencing; PET-CT, positron emission tomography–computed tomography; qPCR, quantitative PCR.

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