Multiple myeloma (MM) is an incurable hematological malignancy characterized by the clonal expansion of tumor plasma cells producing non-functional monoclonal antibodies. The marked genetic and clinical heterogeneity of MM complicates treatment and results in variable therapeutic responses, particularly in relapsed or refractory MM (RRMM), where successive lines of therapy tend to be less effective due to resistance and persistence mechanisms. Minimal residual disease (MRD) is a crucial prognostic factor, with MRD negativity strongly associated with improved progression-free survival (PFS) and overall survival (OS). The evaluation of MRD through circulating clonal plasma cells (CCPCs) has emerged as an informative approach for risk stratification and therapeutic guidance. In this study, we analyzed the prognostic role of CCPCs in 46 RRMM patients undergoing salvage therapy with Daratumumab-based regimens, utilizing multicolor flow cytometry. Results showed that clinical relapse correlated with poorer PFS and OS compared to biochemical relapse. Furthermore, a threshold of 0.04% CCPCs/WBCs in peripheral blood was identified as a marker of poor prognosis, confirming the importance of CCPCs in MRD assessment. Additionally, physical separation methods based on cellular properties such as density, size, and dielectric characteristics are emerging as biomarker-independent alternatives for MRD evaluation. In particular, dielectrophoresis (DEP) and electrorotation (ROT) exploit the electrical properties of cells to distinguish different cell lines. Our findings demonstrated that ROT effectively differentiates MM cells with distinct metabolic profiles and resistance mechanisms, although it is less effective for cells with similar characteristics. These results highlight the potential of electrokinetic techniques, such as DEP and ROT, to characterize MM heterogeneity and improve MRD assessment, opening new perspectives for diagnosis and therapeutic stratification.
Il mieloma multiplo (MM) è una neoplasia ematologica incurabile caratterizzata dall'espansione clonale delle plasmacellule tumorali che producono anticorpi monoclonali non funzionali. È caratterizzato da una marcata eterogeneità genetica e clinica che complicano il trattamento e determinano risposte terapeutiche variabili, in particolare nei casi di MM recidivante o refrattario (RRMM), dove le successive linee di terapia tendono a essere meno efficaci a causa di meccanismi di resistenza e persistenza. La malattia minima residua (MRD) è un fattore prognostico cruciale, con la negatività della MRD fortemente correlata a una maggiore sopravvivenza libera da progressione (PFS) e sopravvivenza globale (OS). Inoltre, la valutazione della MRD attraverso le plasmacellule clonali circolanti (CCPC) è emersa come un approccio informativo per la stratificazione del rischio e la guida terapeutica. Data l’importanza prognostica della valutazione dell’MRD, in questo studio è stata valutata, mediante citometria a flusso multicolore, il ruolo delle CCPC in 46 pazienti con RRMM sottoposti a terapia di salvataggio basata su Daratumumab. I risultati hanno rivelato che la recidiva clinica correla con PFS e una OS peggiori rispetto alla recidiva biochimica, identificando una soglia dello 0,04% di CCPC/WBC come marker di prognosi sfavorevole e confermando l’importanza delle CCPCs nella valutazione della MRD. Oggi, metodi di separazione fisica basati su proprietà cellulari, come densità, dimensioni e caratteristiche dielettriche, sono utilizzati come tecniche alternative indipendenti dai biomarcatori per la valutazione dell’MRD. In particolare, la dielettroforesi (DEP) e l'elettrorotazione (ROT) sfruttano le proprietà elettriche delle cellule per separare o caratterizzare linee cellulari differenti. I nostri risultati dimostrano che la ROT differenzia efficacemente le cellule di MM con profili metabolici e meccanismi di resistenza distinti, ma è meno efficace per cellule con caratteristiche simili. Questi risultati evidenziano il potenziale delle tecniche elettrocinetiche, come DEP e ROT, per caratterizzare l'eterogeneità del MM utile per la valutazione della MRD.
Elettrorotazione e Profilazione Dielettrica: Strategie Avanzate per la Rilevazione della Malattia Minima Residua nel Mieloma Multiplo / Scandura, Grazia. - (2024 Dec 18).
Elettrorotazione e Profilazione Dielettrica: Strategie Avanzate per la Rilevazione della Malattia Minima Residua nel Mieloma Multiplo
SCANDURA, GRAZIA
2024-12-18
Abstract
Multiple myeloma (MM) is an incurable hematological malignancy characterized by the clonal expansion of tumor plasma cells producing non-functional monoclonal antibodies. The marked genetic and clinical heterogeneity of MM complicates treatment and results in variable therapeutic responses, particularly in relapsed or refractory MM (RRMM), where successive lines of therapy tend to be less effective due to resistance and persistence mechanisms. Minimal residual disease (MRD) is a crucial prognostic factor, with MRD negativity strongly associated with improved progression-free survival (PFS) and overall survival (OS). The evaluation of MRD through circulating clonal plasma cells (CCPCs) has emerged as an informative approach for risk stratification and therapeutic guidance. In this study, we analyzed the prognostic role of CCPCs in 46 RRMM patients undergoing salvage therapy with Daratumumab-based regimens, utilizing multicolor flow cytometry. Results showed that clinical relapse correlated with poorer PFS and OS compared to biochemical relapse. Furthermore, a threshold of 0.04% CCPCs/WBCs in peripheral blood was identified as a marker of poor prognosis, confirming the importance of CCPCs in MRD assessment. Additionally, physical separation methods based on cellular properties such as density, size, and dielectric characteristics are emerging as biomarker-independent alternatives for MRD evaluation. In particular, dielectrophoresis (DEP) and electrorotation (ROT) exploit the electrical properties of cells to distinguish different cell lines. Our findings demonstrated that ROT effectively differentiates MM cells with distinct metabolic profiles and resistance mechanisms, although it is less effective for cells with similar characteristics. These results highlight the potential of electrokinetic techniques, such as DEP and ROT, to characterize MM heterogeneity and improve MRD assessment, opening new perspectives for diagnosis and therapeutic stratification.File | Dimensione | Formato | |
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