Monitoring Plasma Cell Dyscrasias With Cell-free DNA Analysis

The analysis of cell-free tumor DNA (cfDNA) has emerged as a promising method to determine the evolving genomic landscape of the whole tumor compartment, mainly in solid malignancies. Plasma cell dyscrasias are characterized by complex and constantly changing genomic aberrations that are important in terms of prognosis, evaluation of the minimal residual disease, and response monitoring. In multiple myeloma, the detection of clonal immunoglobulin rearrangements and driver gene mutations in the cfDNA has shown high concordance rates with their identification in bone marrow-derived tumor DNA. In Waldenström macroglobulinemia, cfDNA can be a reliable alternative to bone marrow aspiration for determining the mutational status of the MYD88 and CXCR4 genes. Importantly, cfDNA can be representative of the whole bone marrow compartment and of extramedullary sites in contrast to the sampling of a single bone marrow site. However, standardization and validation of the techniques are necessary before integrating cfDNA in the clinical practice. Therefore, we encourage the conduction of clinical trials with novel cfDNA-based designs and the adoption of cfDNA-guided endpoints in order to precisely determine the role of cfDNA in the current management of plasma cell dyscrasias.