OAB-059: Towards a comprehensive multimodal minimal residual disease assessment in multiple myeloma: the role of circulating cell-free DNA to define the extent of disease spreading

Liquid biopsy by analysis of circulating myeloma cells and cell-free nucleic acids: a novel noninvasive approach of disease evaluation in multiple myeloma

“…Furthermore, identical subclonal hierarchies were observed in paired BM and plasma samples from patients with MM with ≥ 3 mutations or several mutations in the same gene [3]. In patients with MM, cfDNA and BM samples showed high concordance of CNAs (86.4%-90.5%) [49,74], and most MM-related sCNAs (e.g., 1q gain and 13q deletion) were shared by two samples [46,95]. The can profile from cfDNA produced a corresponding risk classification in 78% of patients with MM as the one obtained from BM clonal PCs based on 1q21 gain and 17p13 deletion [48].…”

“…5) The tumor cell burden in the PB was significantly lower than that in the BM (approximately 40-100 times lower) [5,23,41,44]. Furthermore, cfDNA had significantly lower TF and VAF of tumor-related mutations than the BM [74]. MM in the PB could be missed when the disease burden did not reach the lower limit of the detection method.…”

“…The cfDNA levels were observed to be significant predictors of clinical scores or markers of high disease burden, including advanced ISS stage [9,57,73] and R-ISS stage [46,73], elevated levels of LDH [3,9,47,73] and β2-MG in serum [9], more EM disease in positron emission tomography-computed tomography (PET-CT) [47,74], or osteolytic lesions [48,74]. Most patients showed a positive correlation between the frequencies and VAF of mutations [57,73,75,76], the TF based on CNAs [3,49,74,76], and the frequencies of MM clones (Ig rearrangements) [36] in paired myeloma cells in the BM and cfDNA. However, the ctDNA level only showed a conditional correlation with myeloma cell infiltration in the BM.…”