Abstract

Multiple myeloma (MM) is a treatable plasma cell cancer with no cure. Clinical evidence shows that the status of minimal residual disease (MRD) after treatment is an independent prognostic factor of MM. MRD indicates the depth of post-therapeutic remission. In this review article, we outlined the major clinical trials that have determined the prognostic value of MRD in MM. We also reviewed different methods that were used for MM MRD assessment. Most important, we reviewed our current understanding of MM MRD biology. MRD studies strongly indicate that MRD is not a uniform declination of whole MM tumor population. Rather, MM MRD exhibits unique signatures of cytogenetic aberration and gene expression profiles, unlike those of MM cells before therapy. Diagnostic high-risk MM and low-risk MM exhibited a diversity of MRD features. Clonal evaluation may occur at the MRD stage in MM. The dynamics from the diagnostic MM to MRD correlate with the disease prognosis. Lastly, on the aspect of omics, we performed data-based analysis to address the biological features underlying the course of diagnostic-to-MRD MM. To summarize, the MRD stage of disease represents a critical step in MM pathogenesis and progression. Demonstration of MM MRD biology should help us to deal with the curative difficulties.

Highlights

  • Multiple myeloma (MM) is a hematological cancer characterized by malignant plasma cells accumulation in bone marrow [1]

  • minimal residual disease (MRD) represents a critical stage in MM treatment, during which the patient has a minimal number of resistant tumor cells

  • Both MRD status and the dynamics of diagnosis-to-MRD transition have a prognostic value for MM

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Summary

Introduction

Multiple myeloma (MM) is a hematological cancer characterized by malignant plasma cells accumulation in bone marrow [1]. In the past few decades, the use of autologous stem cell transplantation (ASCT), proteasome inhibitors, and immunomodulatory drugs have revolutionarily extended MM patients’ overall survival (OS) [2–5]. The approval of novel agents, such as CD38 targeting antibodies and XPO1 inhibitors, in MM clinics give patients additional beneficial options [6–10]. Even with the significant improvement of disease management, MM remains incurable. Most MM patients, if not all of them, relapse after treatment [11]. Multiple rounds of therapies and relapse lead to refractory disease and patients lost

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