Defining the undetectable: The current landscape of minimal residual disease assessment in multiple myeloma and goals for future clarity

Multiple Myeloma, the second most prevalent hematologic malignancy, yet lacks an established curative therapy. However, overall response rate to modern four-drug regimens approaches 100%. Major efforts have thus focused on the measurement of minute quantities of residual disease (minimal residual di...

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Bibliographic Details
Published in:Blood reviews 2021-03, Vol.46, p.100732-100732, Article 100732
Main Authors: Diamond, Benjamin T., Rustad, Even, Maclachlan, Kylee, Thoren, Katie, Ho, Caleb, Roshal, Mikhail, Ulaner, Gary A., Landgren, C. Ola
Format: Article
Language:English
Subjects:
Biomarkers, Tumor
Diagnostic Imaging
Disease Management
FDG-PET
Flow cytometry
Flow Cytometry - methods
High-Throughput Nucleotide Sequencing - methods
Humans
Mass Spectrometry - methods
Measurable residual disease
Minimal residual disease
Molecular Diagnostic Techniques - methods
Molecular Diagnostic Techniques - standards
Multiple myeloma
Multiple Myeloma - diagnosis
Multiple Myeloma - etiology
Neoplasm, Residual - diagnosis
Next generation sequencing
Peripheral blood assays
Targeted imaging
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Summary:Multiple Myeloma, the second most prevalent hematologic malignancy, yet lacks an established curative therapy. However, overall response rate to modern four-drug regimens approaches 100%. Major efforts have thus focused on the measurement of minute quantities of residual disease (minimal residual disease or MRD) for prognostic metrics and therapeutic response evaluation. Currently, MRD is assessed by flow cytometry or by next generation sequencing to track tumor-specific immunoglobulin V(D)J rearrangements. These bone marrow-based methods can reach sensitivity thresholds of the identification of one neoplastic cell in 1,000,000 (10−6). New technologies are being developed to be used alone or in conjunction with established methods, including peripheral blood-based assays, mass spectrometry, and targeted imaging. Data is also building for MRD as a surrogate endpoint for overall survival. Here, we will address the currently utilized MRD assays, challenges in validation across labs and clinical trials, techniques in development, and future directions for successful clinical application of MRD in multiple myeloma.
ISSN:0268-960X
1532-1681
DOI:10.1016/j.blre.2020.100732