The utility of non-invasive liquid biopsy for mutational analysis and minimal residual disease assessment in extramedullary multiple myeloma.

Liquid biopsy is a promising technique for tumor genetic profiling and evaluating disease progression. Recent advances in circulating tumor DNA (ctDNA) research highlight its utility in solid tumors and hematological diseases. Extramedullary multiple myeloma (EMM) is an advanced type of multiple myeloma, defined by the presence of clonal plasma cells outside of the bone marrow. The potential of ctDNA to reveal the holistic genomic landscape of EMM is of great interest. Moreover, the mutational concordance between ctDNA and extramedullary plasmacytoma biopsies requires further investigation. In this study, using time-matched extramedullary plasmacytoma biopsies, bone marrow aspirates, and plasma samples from eight EMM patients, we conducted deep sequencing targeting the coding regions of 22 multiple myeloma-related genes. Sequencing results were further verified using droplet digital PCR. Gene mutations in mitogen-activated protein kinase pathways were identified in all 8 tissue biopsies and 7/8 (87.5%) time-matched plasma samples. The ctDNA to tissue biopsy concordance and bone marrow aspirate to tissue biopsy concordance were 0.873 (P = 8.66e−7) and 0.621 (P = 0.109), respectively. In conclusion, our results suggest that ctDNA can be a reliable surrogate for extramedullary plasmacytoma biopsy to characterize the genomic landscape and track disease progression, particularly when extramedullary plasmacytomas are inaccessible. Funding Statement: This work was supported in part by the National Science Foundation for Young Scientists of China (No. 81700160), National Natural Science Foundation of China (General Program, No. 81873452), National Natural Science Foundation of China (Key Program, No. 81630006). Declaration of Interests: The authors stated: No relevant conflicts of interest to declare. Ethics Approval Statement: This study was approved by Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. The approval file number is TJ-IRB20180813.