Those fresh techniques may dramatically change MM MRD assessment in future. Clinical significance of myeloma MRD The depth of remission in MM after therapy is closely related to the prognosis of the disease [32]. occur at the MRD stage in MM. The dynamics from the diagnostic MM to MRD correlate with the disease 3AC prognosis. Lastly, on the aspect of omics, we performed data-based analysis to address the biological features underlying the course of diagnostic-to-MRD MM. To summarize, the MRD stage of disease represents a critical step in RAB7A MM pathogenesis and progression. Demonstration of MM MRD biology should help us to deal with the curative difficulties. Supplementary Information The online version contains supplementary material available at 10.1186/s40364-021-00328-2. measurable residual disease, multiparameter flow cytometry, next-generation flow cytometry, allele-specific oligonucleotide quantitative polymerase chain reaction, next-generation sequencing, positron emission tomography with computed tomography using 18F-deoxyglucose In the past few years, MRD detection techniques have been developed rapidly with 3AC great improvements in sensitivity and applicability. NGS is becoming an important method for MRD detection to guide individualized therapy. In NGS-based MRD assessment, the IgH/IgK/IgL loci are sequenced to capture Ig gene re-arrangements in residual MM cells. The NGS data could be further interpreted to identify subclones, clonal evolution, and cloning tides at the MRD stage [24, 25, 41]. Another trend of MM MRD assessment is to combine NGF, NGS, and PET-CT for comprehensive MRD detection [42, 43]. Since MM is focally distributed in the BM, there is a possibility that the lesion tissue is not obtained in the BM aspiration. In addition, some patients may present extramedullary residual plasma cells after treatment. Whole-body imaging, such as PET-CT or MRI, is able to catch those residual diseases. A recent 3AC study suggests that whole-body diffusion-weighted MRI (WB-DWI-MRI) may provide better MRD assessment than FDG PET-CT [44]. With availability of such functional imaging techniques, the precise evaluation of response has become feasible also for MM lesions in bones and other organs. Thus, intramedullary MRD negativity, determined by MFC or NGS, plus extramedullary WB-DWI-MRI or PET-CT negativity may provide more accurate assessment for deep remission. Of notice, many new techniques for MRD assessment, such as matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) methods [45], liquid chromatography-mass spectrometry (LC-MS) methods [46], circulating cell-free DNA (cfDNA) [47] and single cell RNA-sequencing (scRNA-seq) [48], are currently under investigations at laboratory and pre-clinical stages. Those new techniques may dramatically change MM MRD assessment in future. Clinical significance of myeloma MRD The depth of remission in MM after therapy is closely related to the prognosis of the disease [32]. Therefore, MRD status provides supplementary prognostic stratification in CR MM patients. A series of studies [20, 32, 42, 49C64] showed that MRD negativity was positively associated with prolonged PFS and OS in MM (Table?2). The inclusion criteria of Table?2 data were publications with the key words minimal residual disease, multiple myeloma, and overall survival, while the exclusion criteria were 1) results from meta-analysis and review; 2) study population of less than 100; 3) no survival data; 4) hazard ratios (HRs) were not reported or results were not statistically significant. Based on tight correlation of MRD status of MM treatment outcome, IMWG recommends MRD tests for all MM patients who have achieved CR [15]. The sensitivity of MRD detection affects the prognostic value of MRD [32]. MRD negativity determined by more sensitive methods, such as NGF or NGS, had better prediction of prognosis than that determined by less sensitive methods, such as 4-color MFC [65]. The correlation between MRD and other MM prognostic factors is complicated.