Abstract
Simple SummaryCurrently, response rates in multiple myeloma (MM) have increased dramatically, with more than 50% otablef those who respond satisfying complete response criteria. Achieving frequent deep responses has necessarily led to test conceptual advantages for assessing and treating MM patients with only minimal residual disease (MRD). In this review, we present and discuss the clinical relevance, methodology, and challenges for measuring MRD in MM.The game-changing outcome effect, due to the generalized use of novel agents in MM, has cre-ated a paradigm shift. Achieving frequent deep responses has placed MM among those neoplasms where the rationale for assessing MRD is fulfilled. However, its implementation in MM has raised specific questions: how might we weight standard measures against deep MRD in the emerging CAR-T setting? Which high sensitivity method to choose? Are current response criteria still useful? In this work, we address lessons learned from the use of MRD in other neoplasms, the steps followed for the harmonization of current methods for comprehensively measuring MRD, and the challenges that new therapies and concepts pose in the MM clinical field.
Highlights
The initial definition of a complete remissions (CR) only required less than 5% of plasma cells in the bone marrow (BM), irrespective of their clonal nature. This definition was further refined to stringent CR by the addition of the serum-free light chain ratio assay plus immunohistochemical clonal assessment on the trephine biopsy [15]. These consensus criteria were uniformly incorporated into clinical trials, allowing improved comparisons, and they remained applicable while older therapies were predominant, including autologous stem-cell transplantation (ASCT) when less than half of patients achieved CR [16]
Both this multiparametric flow cytometry (MFC) and an nextgeneration sequencing (NGS) study found that approximately 40% of patients displayed minimal residual disease (MRD) in BM that was undetectable in PB [138,139], underscoring the need for additional analysis to refine the utility of blood in monitoring MM disease
An abstract presented by Carlson et al at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting evaluated the cost-effectiveness of MRD assessment during maintenance treatment for MM patients [144]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Multiple myeloma (MM) remains an incurable disease, median overall survival (OS) for newly diagnosed patients has dramatically improved in the last few decades, and it is closer to 10 years, with increasing proportions of long-term survivors [1]. This substantial progress is mostly due to a number of effective therapies, most of them fulfilling the “targeted agent” definition, an increased knowledge of how to best combine them, and better supportive care. We will follow, as it is not uncommon in our hematology field [6,7,8], a Victorian wedding rhyme, with the poetic license allowing us to alter the order of the “Something blue” and “Something borrowed” verses
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