Blood monitoring of circulating tumor plasma cells by next generation flow in multiple myeloma after therapy

Minimal Residual Disease in Multiple Myeloma: State of the Art and Future Perspectives

“…Available data showed a high concordance in clonal mutations between circulating tumor cells and bone marrow paired samples, with some subclonal mutations being found exclusively in circulating tumor cells [44][45][46]. The NGF assay for MRD evaluation is also feasible and highly sensitive for the detection and enumeration of circulating tumor cells in MM, even though a significant proportion of MM cases that are positive in the bone marrow or at serum immunofixation still had undetectable circulating tumor cells in paired blood samples (40 and 30%, respectively) [47]. Hence, based on current data, both circulating tumor DNA and circulating tumor cells may be used for mirroring the genetic landscape of bone marrow-based disease and recapitulate efficiently the spatial intra-subclonal heterogeneity (particularly for those patients with extramedullary disease), but efforts are needed to improve standardization and increase their sensitivity in order to replace bone marrow MRD assessment.…”

Detection of Circulating Tumor Plasma Cells in Monoclonal Gammopathies: Methods, Pathogenic Role, and Clinical Implications

“…During recent decades, different methods have been developed and used for the detection of CTPC (Graphical abstract [ 19 , 21 , 22 , 23 , 30 , 35 ] and Figure 2 ). Conventional cytology was first used (in combination with complete blood counts obtained in an automated hematology analyzer) for the identification of circulating PC in blood smears of patients diagnosed with monoclonal gammopathy.…”

“…The latter technique allowed for (more specific) assessment of greater numbers of clonal PC in the blood of MM and MGUS patients based on restricted light chain expression by tumor PC [ 19 , 23 ]. In order to further increase the sensitivity and specificity of the above techniques, several different conventional flow cytometry [ 20 , 22 , 31 ] and next generation flow cytometry (NGF) procedures [ 21 , 35 ], together with polymerase chain reaction (PCR)-based, e.g., allele-specific oligonucleotide (ASO) quantitative PCR (qPCR) [ 19 , 113 ] and next generation sequencing (NGS) [ 114 ] techniques, were subsequently developed and tested. In addition to differences in the sensitivity reported for the above flow vs. molecular techniques, the results obtained so far are also influenced by the type of material analyzed (e.g., inclusion of nucleic acid from non-viable cells in molecular techniques) and/or the way patients were selected for analysis (e.g., inclusion of patients that reached no response or partial response together with complete response cases).…”

“…From a clinical point of view, the presence and number of CTPC has been proven to have both diagnostic and prognostic implications in MGUS [ 21 , 23 ], SMM [ 24 , 25 , 26 ] and in symptomatic MM [ 20 , 21 , 27 , 28 , 29 , 30 , 31 ] patients. In addition, detection of CTPC has proven useful for (closer) minimally-invasive monitoring of MM after therapy [ 32 , 33 , 34 , 35 ]. Despite this, the reported frequency of MM and MGUS cases with detectable CTPC varies significantly, depending on the specific methodology used and its sensitivity and specificity.…”

“…Despite this, the reported frequency of MM and MGUS cases with detectable CTPC varies significantly, depending on the specific methodology used and its sensitivity and specificity. Thereby, usage of highly-sensitive and standardized techniques for the detection and quantitation of CTPC becomes critically important [ 21 , 35 ]. Here, we provide a detailed review of the currently available techniques for the detection of CTPC in patients with plasma cell neoplasms, their biological features, pathogenic role, and clinical relevance, with special focus on MGUS and MM patients.…”