Current and Upcoming Diagnostics and Prognostics in Multiple Myeloma

A special issue of Hemato (ISSN 2673-6357). This special issue belongs to the section "Plasma Cell Disorders".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 19070

Special Issue Editor


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Guest Editor
1. Oslo Myeloma Center, Oslo University Hospital, Oslo, Norway
2. KG Jebsen Center for B Cell Malignancies, University of Oslo, Oslo, Norway
Interests: clinical studies in myeloma; PET-CT; MRD-driven trials

Special Issue Information

Dear colleagues,

The development of diagnostic and prognostic procedures in multiple myeloma is progressing with significant pace, giving deeper and more substantial information for myeloma patients. The genetic constitution of the clonal plasma cells, analyzed from bone marrow, circulating cells and DNA, as well as the increased information from developing radiological and nuclear-medicine methods, will enable more personalized treatment and follow-up in the future. Our methods of follow-up are also advancing, with more sensitive techniques of measuring minimal residual disease (MRD) laying the ground for studies intensifying and de-intensifying treatment according to the response status of the patient.

In this Special Issue, we trail the current and future statuses of these topics, showing where we are and where we are going.

Dr. Fredrik Schjesvold
Guest Editor

Manuscript Submission Information

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Keywords

  • MRD (minimal residual disease)
  • PET (positron emission tomography)
  • Mass-spec
  • Mutations
  • FISH (fluorescent in situ hybridization)
  • DW-MRI (diffusion-weighted magnetic resonance imaging)

Published Papers (6 papers)

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Review

12 pages, 895 KiB  
Review
Minimal Residual Disease in Multiple Myeloma—Current Approaches and Future Clinical Implications
by Theresia Akhlaghi, Ross Firestone and Malin Hultcrantz
Hemato 2022, 3(3), 454-465; https://doi.org/10.3390/hemato3030031 - 19 Jul 2022
Cited by 2 | Viewed by 2870
Abstract
The prognosis and clinical outcomes for patients with multiple myeloma have improved significantly over the past two decades. A substantial number of patients now achieve complete remission after induction therapy, and more sensitive methods are needed to assess response. Minimal or measurable residual [...] Read more.
The prognosis and clinical outcomes for patients with multiple myeloma have improved significantly over the past two decades. A substantial number of patients now achieve complete remission after induction therapy, and more sensitive methods are needed to assess response. Minimal or measurable residual disease (MRD) has been incorporated in many clinical trials as well as in clinical practice. The importance of MRD assessment and correlation between MRD negativity and prolonged progression-free and overall survival has been confirmed in numerous clinical trials and several meta-analyses. Recent studies have even suggested that MRD negativity can partly overcome the impact of the negative prognostic factors such as high-risk cytogenetics or adverse revised international scoring system (R-ISS) stage. MRD can be measured in the bone marrow via imaging and via emerging blood-based techniques. The most common methods are multicolor flow cytometry and next-generation sequencing of bone marrow samples. Using these methods in optimal settings, MRD negativity with a sensitivity level of 10−6 can be detected. In this review, we discuss the benefits and limitations of these techniques as well as the clinical implications. Full article
(This article belongs to the Special Issue Current and Upcoming Diagnostics and Prognostics in Multiple Myeloma)
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11 pages, 262 KiB  
Review
What Is Genomic High-Risk Myeloma?
by Faith E. Davies and Brian A. Walker
Hemato 2022, 3(2), 287-297; https://doi.org/10.3390/hemato3020021 - 05 Apr 2022
Cited by 1 | Viewed by 2678
Abstract
Although treatment of multiple myeloma has changed dramatically over time, there is still a subpopulation of patients who do not respond to treatments and are labeled as high risk. A combination of serum and genomic markers can be used to identify and stratify [...] Read more.
Although treatment of multiple myeloma has changed dramatically over time, there is still a subpopulation of patients who do not respond to treatments and are labeled as high risk. A combination of serum and genomic markers can be used to identify and stratify these patients according to associations with outcome. The most common method of identifying the genomic markers of high-risk multiple myeloma is using fluorescence in situ hybridization using probes to identify IgH translocations or copy number changes including the t(4;14), t(14;16), t(14;20), gain 1q, and del(17p). However, as research studies utilize newer technologies, such as whole genome sequencing, more high-risk factors are being identified including mutations of TP53, DIS3, BRAF, and complex structural events. Integration of comprehensive genomic studies into clinical trials will aid in defining the genomic high-risk landscape of multiple myeloma, which in turn can be transferred to individual patient diagnostics and treatment management. Full article
(This article belongs to the Special Issue Current and Upcoming Diagnostics and Prognostics in Multiple Myeloma)
19 pages, 363 KiB  
Review
Is Circulating DNA and Tumor Cells in Myeloma the Way Forward?
by Emilie Arnault Carneiro, Filipa Barahona, Carolina Pestana and Cristina João
Hemato 2022, 3(1), 63-81; https://doi.org/10.3390/hemato3010006 - 13 Jan 2022
Cited by 1 | Viewed by 2918
Abstract
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. [...] Read more.
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. Full article
(This article belongs to the Special Issue Current and Upcoming Diagnostics and Prognostics in Multiple Myeloma)
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Graphical abstract

5 pages, 204 KiB  
Review
Will Mass Spectrometry Replace Current Techniques for Both Routine Monitoring and MRD Detection in Multiple Myeloma?
by Katie L. Thoren
Hemato 2021, 2(4), 764-768; https://doi.org/10.3390/hemato2040052 - 09 Dec 2021
Cited by 2 | Viewed by 2351
Abstract
In recent years, mass spectrometry has been increasingly used for the detection of monoclonal proteins in serum. Mass spectrometry is more analytically sensitive than serum protein electrophoresis and immunofixation, can help distinguish therapeutic monoclonal antibodies from M-proteins, and can detect the presence of [...] Read more.
In recent years, mass spectrometry has been increasingly used for the detection of monoclonal proteins in serum. Mass spectrometry is more analytically sensitive than serum protein electrophoresis and immunofixation, can help distinguish therapeutic monoclonal antibodies from M-proteins, and can detect the presence of post-translational modifications. Mass spectrometry also shows promise as a less-invasive, peripheral-blood-based test for detecting minimal residual disease in multiple myeloma. Studies comparing the clinical utility of mass spectrometry to current blood- and bone-marrow-based techniques have been conducted. Although still primarily limited to research settings, clinical laboratories are starting to adopt this technique for patient care. This review will discuss the current status of mass spectrometry testing for multiple myeloma, the benefits and challenges of this technique, and how it may be incorporated into clinical practice in the future. Full article
(This article belongs to the Special Issue Current and Upcoming Diagnostics and Prognostics in Multiple Myeloma)
12 pages, 1021 KiB  
Review
New Targets for PET Imaging of Myeloma
by Mona-Elisabeth Revheim, Caroline Stokke, Jakob Nordberg Nørgaard, Hilde Feiring Phillips, Alexander Gul Sherwani, Fredrik Schjesvold and James P. Connelly
Hemato 2021, 2(4), 727-738; https://doi.org/10.3390/hemato2040049 - 02 Dec 2021
Cited by 3 | Viewed by 4622
Abstract
Recent advances in the treatment of multiple myeloma (MM) have increased the need for accurate diagnosis and detection of minimal residual disease (MRD), disease characterization and localization, and response evaluation and prognostication. Positron emission tomography (PET)/computed tomography (CT) imaging combines molecular and morphological [...] Read more.
Recent advances in the treatment of multiple myeloma (MM) have increased the need for accurate diagnosis and detection of minimal residual disease (MRD), disease characterization and localization, and response evaluation and prognostication. Positron emission tomography (PET)/computed tomography (CT) imaging combines molecular and morphological information and has been shown to be especially valuable in this disease. The most frequently used PET tracer in MM is the glucose analog 18F-fluorodeoxyglucose ([18F]FDG). [18F]FDG PET/CT has a sensitivity for detection of MM between 80% to 100% and is currently the main imaging modality for assessing treatment response and for determining MRD. However, 18F-FDG PET/CT has some limitations, and imaging with alternative tracers that may overcome these constraints should be further explored. This article discusses new targets for PET/CT imaging in the assessment of MM. Full article
(This article belongs to the Special Issue Current and Upcoming Diagnostics and Prognostics in Multiple Myeloma)
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8 pages, 893 KiB  
Review
Diffusion-Weighted MRI—The Way Forward for MRI in Myeloma?
by Jens Hillengass, Maximilian Merz, Ronald Alberico and Majid Chalian
Hemato 2021, 2(4), 672-679; https://doi.org/10.3390/hemato2040044 - 12 Nov 2021
Viewed by 2828
Abstract
Multiple myeloma and other plasma cell disorders infiltrate the bone marrow in different patterns. While some patients show a homogeneous distribution of the clonal plasma cells others present with focal accumulations, commonly called focal lesions. Novel imaging techniques can provide information on these [...] Read more.
Multiple myeloma and other plasma cell disorders infiltrate the bone marrow in different patterns. While some patients show a homogeneous distribution of the clonal plasma cells others present with focal accumulations, commonly called focal lesions. Novel imaging techniques can provide information on these infiltration patterns and, due to their low invasiveness, can be performed repeatedly and therefore be used for monitoring. Conventional magnetic resonance imaging (MRI) has a high sensitivity for bone marrow assessment but cannot safely differentiate between active and inactive lesions. Therefore, positron emission tomography, especially combined with computed tomography (PET/CT), has been more widely used, at least for the monitoring of treatment response. Comparative, but mostly retrospective studies, have shown that functional MRI techniques, namely diffusion-weighted imaging (DWI), which assesses the movement of water molecules, can evaluate tissue cellularity with high sensitivity, which challenges the dominance of PET/CT in treatment response assessment. This review will discuss the benefits and challenges of DWI and compare it to other available imaging techniques used in patients with monoclonal plasma cell disorders. Full article
(This article belongs to the Special Issue Current and Upcoming Diagnostics and Prognostics in Multiple Myeloma)
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