Table 4.

Comparison between different techniques for detection of Minimal Residual Disease in Multiple Myeloma (Adapted from [116,137])

Method	Sample Type	Applicability	Sensitivity	Quantification	Clonal Evolution	Advantage	Limitations
NGS	Nucleic acid (DNA)	~90%	10-6	Absolute	Detectable	Provides information on background repertoire	Not standardized, no guidelines for analysis and data interpretation, available in few labs, Expensive
Flow Cytometry (Next Gen. Flow)	BMA (Cells)	90-100%	3-4 colors-10-3/10-4	Absolute	Not applicable	Fast, reproducible, Accurate quantification well standardized, cost-effective	Large cell number needed (~6 million), Processing to be done on fresh samples
			6-8 colors-10-4
			8-10 colors-10-5
ASO-qPCR	Nucleic acid (DNA)	~80%	10-5	Absolute	Not detected	More sensitive and specific than MFC, fresh sample not required, provides information on background repertoire	More time consuming and relatively laborious, requires patient specific primers, need of a bioinformatics analysis, Expensive
ddPCR	Nucleic acid (DNA)	Not reported	10-4/10-5	Absolute	Not detected	Standard curve Not needed, easy to perform	Dependent on ASO-primer, not standardized, no guidelines for analysis, data interpretation, Expensive
RT-qPCR	Nucleic acid (DNA)	90-95%	10-4/10-5	Absolute	Not detected	Well standardized, International guidelines for analysis and data interpretation	Dependent on ASO-primer, laborious, time consuming, affected by clonal evolution, large amount of diagnostic DNA, Expensive