Liquid biopsy: an evolving paradigm for the biological characterisation of plasma cell disorders

Mithraprabhu, Sridurga; Chen, Maoshan; Savvidou, Ioanna; Reale, Antonia; Spencer, Andrew

doi:10.1038/s41375-021-01339-6

Cited by 25 publications

(25 citation statements)

References 94 publications

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“…Furthermore, patchy-multifocal infiltration of the BM can introduce false-negative results in the biopsy pull if the most disease-heavy spot is missed. To tackle these issues, "liquid biopsy" methods for detection of either residual cells (e.g., circulating malignant plasma cells, cell-free DNA) or trace quantities of M protein are being developed, offering the added advantage of routine testing without the need for invasive procedures (29). Unfortunately, existing NGF or NGS approaches for MRD detection in the BM have suffered from issues of low sensitivity and poor concordance across assays when used in peripheral blood (30,31).…”

Section: Blood-based Methodsmentioning

confidence: 99%

Minimal Residual Disease Assessment in Multiple Myeloma Patients: Minimal Disease With Maximal Implications

Charalampous

Kourelis

2022

Front. Oncol.

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Multiple Myeloma (MM), the second most common hematologic malignancy, has been the target of many therapeutic advances over the past two decades. The introduction of novel agents, such as proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, along with autologous hematopoietic stem cell transplantation (ASCT) in the current standard of care, has increased the median survival of myeloma patients significantly. Nevertheless, a curative treatment option continues to elude us, and MM remains an incurable disease, with patients relapsing even after achieving deep conventionally defined responses, underscoring the need for the development of sensitive methods that will allow for proper identification and management of the patients with a higher probability of relapse. Accurate detection of Minimal Residual Disease (MRD) from a bone marrow biopsy represents a relatively new approach of evaluating response to treatment with data showing clear benefit from obtaining MRD(-) status at any point of the disease course. As life expectancy for patients with MM continues to increase and deep responses are starting to become the norm, establishing and refining the role of MRD in the disease course is more relevant than ever. This review examines the different methods used to detect MRD and discusses future considerations regarding the implementation in day-to-day clinical practice and as a prospective primary endpoint for clinical trials.

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Section: Blood-based Methodsmentioning

confidence: 99%

Minimal Residual Disease Assessment in Multiple Myeloma Patients: Minimal Disease With Maximal Implications

Charalampous

Kourelis

2022

Front. Oncol.

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“…Moreover, parallel analyses of different types of MM liquid biopsies using NGS techniques have been reported before [ 23 , 24 ]. However, we are not aware of any studies [ 25 ] that directly compared a molecular (NGS) and a cell-based (MFC) approach to detect MM in the pB to each other and to standard serologic monitoring. In this work, we present two novel technical modifications of pB-based methods for the detection of MM.…”

Section: Introductionmentioning

confidence: 99%

Monitoring multiple myeloma in the peripheral blood based on cell-free DNA and circulating plasma cells

et al. 2022

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With the advent of novel, highly effective therapies for multiple myeloma (MM), classical serologic monitoring appears insufficient for response assessment and prediction of relapse. Moreover, serologic studies in MM are hampered by interference of therapeutic antibodies. The detection of malignant plasma cell clones by next generation sequencing (NGS) or multiparameter flow cytometry (MFC) circumvents these difficulties and can be performed in the peripheral blood (pB) by targeting circulating cell-free DNA (cfDNA) or circulating plasma cells (CPCs), thus also avoiding an invasive sampling procedure. Here, we applied NGS of VJ light chain (LC) rearrangements in cfDNA and MFC of magnetically-enriched CD138-positive CPCs (me-MFC) to investigate disease burden in unselected MM patients. Sequencing was successful for 114/130 (87.7%) cfDNA samples and me-MFC results were analyzable for 196/205 (95.6%) samples. MM clones were detectable in 38.9% of samples taken at initial diagnosis or relapse (ID/RD), but only in 11.8% of samples taken during complete remission (CR). Circulating MM plasma cells were present in 83.3% of ID/RD samples and 9.9% of CR samples. Residual disease assessment by NGS or me-MFC in samples taken during very good partial remission or CR was 80% concordant. Notably, 4/4 (NGS) and 5/8 (me-MFC) positive CR samples were from patients with oligo- or non-secretory myeloma. The time to progression was shorter if there was evidence of residual myeloma in the pB. Together, our findings indicate that our two novel analytical approaches accurately indicate the course of MM and may be particularly valuable for monitoring patients with serologically non-trackable disease.

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“…Among the chemical entities of biomarkers, RNA plays a prominent role because RNA is thought to monitor the current status of gene expression, i.e., the relevant transcriptome. In the case of blood, circulating cell-associated, vesicle-associated, and cell-free RNA seems to reflect the patterns of current gene expression of the organism, individual organs, and include transcripts originating from malignant cell growth [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Sampling, Logistics, and Analytics of Urine for RT-qPCR-based Diagnostics

Far

Frank

Sczakiel

2021

Cancers

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Body fluids in the context of cancer diagnosis are the primary source of liquid biopsy, i.e., biomarker detection that includes blood and serum, urine, and saliva. RNA represents a particular class of biomarkers because it is thought to monitor the current status of gene expression in humans, in organs, and if present, also in tumors. In case of bladder cancer, we developed a scheme that describes, in detail, all steps from the collection of urine samples from patients, stabilization of samples, their transportation, storage, and marker analysis by qPCR-based technology. We find that urine samples prepared according to this protocol show stability of RNA over more than 10 days at unchilled temperatures during shipping. A specific procedure of primer design and amplicon evaluation allows a specific assignment of PCR products to human genomics and transcriptomics data collections. In summary, we describe a technical option for the robust acquisition of urine samples and the quantitative detection of RNA-based tumor markers in case of bladder cancer patients. This protocol is for general use, and we describe that it works for any RNA-based tumor marker in urine of cancer patients.

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Liquid biopsy: an evolving paradigm for the biological characterisation of plasma cell disorders

Cited by 25 publications

References 94 publications

Minimal Residual Disease Assessment in Multiple Myeloma Patients: Minimal Disease With Maximal Implications

Minimal Residual Disease Assessment in Multiple Myeloma Patients: Minimal Disease With Maximal Implications

Monitoring multiple myeloma in the peripheral blood based on cell-free DNA and circulating plasma cells

Sampling, Logistics, and Analytics of Urine for RT-qPCR-based Diagnostics

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