The Minimal Residual Disease Using Liquid Biopsies in Hematological Malignancies

SIMPLE SUMMARY: Monitoring the response to treatment in hematologic malignancies is essential in defining the best way to optimize patient management. In general, achieving a deeper response has been shown to lead to a better prognosis, and the techniques used to study the minimal residual disease (MRD) are becoming more precise. The use of liquid biopsies, that is, analyzing the presence of alterations in nucleic acids, usually in peripheral blood or other biological fluids, is being studied and optimized with increasingly innovative molecular techniques, such as next-generation sequencing (NGS) in the monitoring of the MRD, avoiding, in many cases, more invasive tests in different hematological neoplasms. Currently, liquid biopsies are not standardized for the MRD monitoring, but there is increasing evidence of its correlation with other techniques to measure responses to treatments and patient outcomes. ABSTRACT: The study of cell-free DNA (cfDNA) and other peripheral blood components (known as “liquid biopsies”) is promising, and has been investigated especially in solid tumors. Nevertheless, it is increasingly showing a greater utility in the diagnosis, prognosis, and response to treatment of hematological malignancies; in the future, it could prevent invasive techniques, such as bone marrow (BM) biopsies. Most of the studies about this topic have focused on B-cell lymphoid malignancies; some of them have shown that cfDNA can be used as a novel way for the diagnosis and minimal residual monitoring of B-cell lymphomas, using techniques such as next-generation sequencing (NGS). In myelodysplastic syndromes, multiple myeloma, or chronic lymphocytic leukemia, liquid biopsies may allow for an interesting genomic representation of the tumor clones affecting different lesions (spatial heterogeneity). In acute leukemias, it can be helpful in the monitoring of the early treatment response and the prediction of treatment failure. In chronic lymphocytic leukemia, the evaluation of cfDNA permits the definition of clonal evolution and drug resistance in real time. However, there are limitations, such as the difficulty in obtaining sufficient circulating tumor DNA for achieving a high sensitivity to assess the minimal residual disease, or the lack of standardization of the method, and clinical studies, to confirm its prognostic impact. This review focuses on the clinical applications of cfDNA on the minimal residual disease in hematological malignancies.