Predicting Treatment Response of Multiple Myeloma Patients Using Tumor Specific cell-free DNA

Great progress achieved in treatment of multiple myeloma (MM) over the past decade changed overall perception of importance of minimal residual disease (MRD) assessment. Since new drugs induce deep responses, MRD must be evaluated using sensitive techniques, such as allele specific PCR (ASO-PCR), next-generation sequencing (NGS) or flow cytometry. MM is a genetically heterogeneous disease characterized by multiple focal lesions in the bone marrow (BM). BM samples are typically used for analysis, but currently an alternative approach called liquid biopsies, which utilize body fluids for analysis of various molecules and cells, is intensively studied. Cell-free DNA as one type of the molecule which can be analyzed using liquid biopsy approach. In our study, patient-specific, clonotypic rearrangement of immunoglobulin heavy chain (IgH) gene, identified in BM samples, was used for qPCR analysis of cfDNA samples from peripheral blood. We demonstrate that dynamics and quantity of patient-specific, clonotypic IgH rearrangement found in cfDNA can predict the outcomes and response of MM patients.