Arnault Carneiro, EmilieBarahona, FilipaPestana, CarolinaJoão, Cristina2023-12-052023-12-052022-03PURE: 77747387PURE UUID: bdb2145c-bf90-4d6c-b73e-79934c17c73cScopus: 85177730452http://hdl.handle.net/10362/160927Funding Information: This research was funded by the Champalimaud Foundation; by the Fundação para a Ciência e Tecnologia—FCT (Research Grant PTDC/MEC-HEM/30315/2017). Publisher Copyright: © 2022 by the authors.Multiple myeloma (MM) is the second deadliest hematological cancer. Despite the enormous innovation on MM treatment in the last decades, still 48% of patients die within 5 years after diagnosis. MM diagnosis and therapeutic strategy mainly rely on direct bone marrow (BM) assessment. Given the MM heterogeneity, BM biopsies do not accurately reflect the whole disease status, hampering accurate disease prognosis. Moreover, biopsies are painful and invasive procedures, highlighting the need for non-invasive and more accurate source of biomarkers. Liquid biopsies are promising sources of biomarkers that may overcome these limitations. Peripheral blood carries circulating myeloma components that are being extensively explored since the last few years as an alternative to BM aspirates. These include circulating tumor cells (CTC), cell-free DNA (cfDNA), and extracellular vesicles containing miRNA and proteins. The current review summarizes scientific evidence establishing BM as a gold standard for the diagnosis, prognosis, and evaluation of minimal residual disease. We discuss the last advances regarding cfDNA and CTC biomarkers from peripheral blood in patients with MM as well as the statistical validations. This paper addresses the technological hurdles associated with liquid biopsies and examines the missing steps for their inclusion into the clinical practice.19371944engbiomarker validationcell-free DNAcirculating tumor plasma celldiagnosisliquid biopsiesminimal residual diseasemultiple myelomaprognosisstatistical assessmentHematologySDG 3 - Good Health and Well-beingreview10.3390/hemato3010006https://www.scopus.com/pages/publications/85177730452