Table 1 Advantages and disadvantages of MRD detection methods

MFC

--- Identification of MM cells by Flow cytometry analysis of MM-specific cell surface antigens.

10^− 4

(4–6 colour)

10^− 5

(8–10 colour)

1) Strong applicability (90–100%)

2) Fast, economical and efficient;

3) Built-in evaluation of sample quality;

4) Not affected by SHM and clonal evolution.

1) Need to be tested within 24-48 h;

2) Data analysis needs professional knowledge and technology;

3) Complex data visualization;

4) Cannot detect cytogenetic characteristics.

NGF

---Optimized version of MFC with higher sensitivity.

10⁻⁶

1) Nearly 100% applicability;

2) EuroFlow Consortium standardization;

3) Highly automated;

4) Based on the analysis of large numbers of cells;

1) Need to be tested within 24-48 h;

2) Cannot detect clonal evolution;

3) Complex data analysis.

ASO-qPCR

---Identification of MM cells by amplifying MM-specific immunoglobulin gene rearrangement.

10⁻⁵

1) Wide range of applications (it can be used in almost all laboratories);

2) Fully standardized detection method and data interpretation standards;

3) No need to process bone marrow samples immediately;

1) The applicability is reduced to 42–75% when using universal primers;

2) The construction of a standard curve will consume a large number of limited bone marrow DNA samples;

3) May provide false negative results.

NGS

--- Identification of MM cells by sequencing the IGH/IGK/IGL loci.

10⁻⁶

1) No need to process samples immediately and no need for a standard curve;

2) Can capture almost all Ig gene rearrangements;

3) Uses consensus primers for clonality detection and subsequent MRD analysis;

4) Adaptive Biotechnologies

(Seattle, WA, US) standardization;

1) May be affected by SHM;

2) No sample built-in test;

3) It is time-consuming, labor-intensive, expensive, and cannot be universally used in clinics and laboratories;

4) Interpretation of results is really difficult, requiring high expertise.

FDG-PET/CT

--- Identification of MM cells by assessing tumor metabolic aberration

Spatial resolution limit of approximately 5 mm

1) Residual active clonal plasma cells can be detected in residual osteolytic lesions;

2) Accurately maps the sites of bone and extra-medullary disease;

3) It is complementary to cellular or molecular-based techniques;

1) May provide false positive results, for example: recent use of chemotherapy or/and growth factors to induce bone marrow reconstitution;

2) May provide false negative results, for example: lack of hexokinase enzyme or use of high-dose steroids;

3) Significant cost.