Non-invasive molecular monitoring in multiple myeloma patients using cell-free tumor DNA: a pilot study

Novel treatments for multiple myeloma (MM) have increased rates of complete response raising interest in more accurate methods to evaluate residual disease. Cell-free tumor DNA (cfDNA) analysis may represent a minimally invasive approach complementary to multiparameter flow cytometry (MFC) and molecular methods on bone marrow aspirates. A sequencing approach using the Ion Torrent Personal Genome Machine was applied to identify clonal immunoglobulin heavy chain (IGH) gene rearrangements in tumor plasma cells (PCs) and in serial plasma samples of 25 MM patients receiving second-line therapy. The same clonal IGH rearrangement identified in tumor PCs was detected in paired plasma samples and levels of IGH cfDNA correlated with outcome and mirrored tumor dynamics evaluated using conventional laboratory parameters. In addition IGH cfDNA levels reflected the number of PCs enumerated by MFC immunophenotyping even in the complete response context. Minimal residual disease negative patients by MFC were characterized by low frequencies of tumor clonotypes in cfDNA and longer survival. This pilot study supports the clinical applicability of the non-invasive monitoring of tumor levels in plasma samples of MM patients by IGH sequencing.