Special Issue "The Asymptomatic Version of Myeloma: MGUS and Smoldering Myeloma"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (29 February 2020).

Special Issue Editor

Prof. Dr. María Victoria Mateos
Website
Guest Editor
1. Senior research, Cancer Research Center/IBMCC, 37007 Salamanca, Spain
2. Hematology Department, University Hospital of Salamanca, Paseo San Vicente 58-182, 37007 Salamanca, Spain
3. Institute for Biomedical Research of Salamanca, Salamanca 37007, Spain
Interests: myeloma; asymptomatic myeloma; minimal residual disease; early treatment; novel drugs

Special Issue Information

Dear Colleagues,

All cases of multiple myeloma (MM) are preceded by precursor states termed monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). MGUS is present in approximately 3%­–4% of the general population over the age of 50, and it is associated with a risk of progression to MM or related disorder at a rate of 1% per year. SMM accounts for approximately 10% of all MMs, and the risk or progression to MM is not uniform, ranging from 1% to 10% per year. Both plasma cell disorders are asymptomatic with absence of myeloma-related events, and the cutoff of serum M spike is 3 g/dl or bone marrow plasma cell infiltration of 10% for distinguishing both entities. These criteria are useful in clinical practice, and in the SMM field, some models have emerged to identify different risk subgroups of patients that lead to the proposal of clinical trials in SMM patients at high risk of progression to MM with the attempt of delaying the MM development. Positive results have so far been reported which resulted, in 2014, in the update of the diagnostic criteria for MM, including some SMM patients with an imminent risk of progression to MM identified through the presence of some biomarkers. However, in spite of these major advances, our understanding of the pathogenesis of MGUS and SMM and how they can evolve to MM remains incomplete, and emerging insights in the biology of these preneoplastic lesions and their transition to clinical malignancy are crucial to understand the biology of the disease that can potentially contribute to make clinical decisions about the optimal approach for the management of these premalignant diseases.

This Special Issue aims to deepen the mechanisms involved in the transition from MGUS and SMM to MM and how they can be incorporated to the clinical models and how this approach might impact on the management of MGUS and SMM and which patients would be candidates to preventive versus curative approaches.

Dr. María Victoria Mateos
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Monoclonal gammopathy
  • Smoldering myeloma
  • Prognostic features
  • Genetic abnormalities
  • Microenvironment
  • Immune system

Published Papers (5 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
Application of Next-Generation Sequencing for the Genomic Characterization of Patients with Smoldering Myeloma
Cancers 2020, 12(5), 1332; https://doi.org/10.3390/cancers12051332 - 23 May 2020
Abstract
Genomic analysis could contribute to a better understanding of the biological determinants of the evolution of multiple myeloma (MM) precursor disease and an improved definition of high-risk patients. To assess the feasibility and value of next-generation sequencing approaches in an asymptomatic setting, we [...] Read more.
Genomic analysis could contribute to a better understanding of the biological determinants of the evolution of multiple myeloma (MM) precursor disease and an improved definition of high-risk patients. To assess the feasibility and value of next-generation sequencing approaches in an asymptomatic setting, we performed a targeted gene mutation analysis and a genome-wide assessment of copy number alterations (CNAs) by ultra-low-pass whole genome sequencing (ULP-WGS) in six patients with monoclonal gammopathy of undetermined significance and 25 patients with smoldering MM (SMM). Our comprehensive genomic characterization highlighted heterogeneous but substantial values of the tumor fraction, especially in SMM; a rather high degree of genomic complexity, in terms of both mutations and CNAs, and inter-patient variability; a higher incidence of gene mutations and CNAs in SMM, confirming ongoing evolution; intraclonal heterogeneity; and instances of convergent evolution. ULP-WGS of these patients proved effective in revealing the marked genome-wide level of their CNAs, most of which are not routinely investigated. Finally, the analysis of our small SMM cohort suggested that chr(8p) deletions, the DNA tumor fraction, and the number of alterations may have clinical relevance in the progression to overt MM. Although validation in larger series is mandatory, these findings highlight the promising impact of genomic approaches in the clinical management of SMM. Full article
(This article belongs to the Special Issue The Asymptomatic Version of Myeloma: MGUS and Smoldering Myeloma)
Show Figures

Figure 1

Open AccessArticle
Characteristics of MGUS and Multiple Myeloma According to the Target of Monoclonal Immunoglobulins, Glucosylsphingosine, or Epstein-Barr Virus EBNA-1
Cancers 2020, 12(5), 1254; https://doi.org/10.3390/cancers12051254 - 15 May 2020
Abstract
Chronic stimulation by infectious or self-antigens initiates subsets of monoclonal gammopathies of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple myeloma (MM). Recently, glucosylsphingosine (GlcSph) was reported to be the target of one third of monoclonal immunoglobulins (Igs). In this study of [...] Read more.
Chronic stimulation by infectious or self-antigens initiates subsets of monoclonal gammopathies of undetermined significance (MGUS), smoldering multiple myeloma (SMM), or multiple myeloma (MM). Recently, glucosylsphingosine (GlcSph) was reported to be the target of one third of monoclonal immunoglobulins (Igs). In this study of 233 patients (137 MGUS, 6 SMM, 90 MM), we analyzed the GlcSph-reactivity of monoclonal Igs and non-clonal Igs. The presence of GlcSph-reactive Igs in serum was unexpectedly frequent, detected for 103/233 (44.2%) patients. However, GlcSph was targeted by the patient’s monoclonal Ig for only 37 patients (15.9%); for other patients (44 MGUS, 22 MM), the GlcSph-reactive Igs were non-clonal. Then, the characteristics of patients were examined: compared to MM with an Epstein-Barr virus EBNA-1-reactive monoclonal Ig, MM patients with a GlcSph-reactive monoclonal Ig had a mild presentation. The inflammation profiles of patients were similar except for moderately elevated levels of 4 cytokines for patients with GlcSph-reactive Igs. In summary, our study highlights the importance of analyzing clonal Igs separately from non-clonal Igs and shows that, if autoimmune responses to GlcSph are frequent in MGUS/SMM and MM, GlcSph presumably represents the initial pathogenic event for ~16% cases. Importantly, GlcSph-initiated MM appears to be a mild form of MM disease. Full article
(This article belongs to the Special Issue The Asymptomatic Version of Myeloma: MGUS and Smoldering Myeloma)
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
Treatment of Smoldering Multiple Myeloma: Ready for Prime Time?
Cancers 2020, 12(5), 1223; https://doi.org/10.3390/cancers12051223 - 13 May 2020
Abstract
The current standard of care for smoldering multiple myeloma (SMM) is observation until there is end-organ involvement. With newer and more effective treatments available, a question that is increasingly asked is whether early intervention in patients with SMM will alter the natural history [...] Read more.
The current standard of care for smoldering multiple myeloma (SMM) is observation until there is end-organ involvement. With newer and more effective treatments available, a question that is increasingly asked is whether early intervention in patients with SMM will alter the natural history of their disease. Herein, we review the evolving definition of SMM and risk stratification models. We discuss evidence supporting early intervention for SMM—both as a preventative strategy to delay progression and as an intensive treatment strategy with a goal of potential cure. We highlight ongoing trials and focus on better defining who may require early intervention. Full article
(This article belongs to the Special Issue The Asymptomatic Version of Myeloma: MGUS and Smoldering Myeloma)
Open AccessReview
PD-L1–PD-1 Pathway in the Pathophysiology of Multiple Myeloma
Cancers 2020, 12(4), 924; https://doi.org/10.3390/cancers12040924 - 10 Apr 2020
Abstract
PD-L1 expressed on tumor cells contributes to disease progression with evasion from tumor immunity. Plasma cells from multiple myeloma (MM) patients expressed higher levels of PD-L1 compared with healthy volunteers and monoclonal gammopathy of undetermined significance (MGUS) patients, and its expression is significantly [...] Read more.
PD-L1 expressed on tumor cells contributes to disease progression with evasion from tumor immunity. Plasma cells from multiple myeloma (MM) patients expressed higher levels of PD-L1 compared with healthy volunteers and monoclonal gammopathy of undetermined significance (MGUS) patients, and its expression is significantly upregulated in relapsed/refractory patients. Furthermore, high PD-L1 expression is induced by the myeloma microenvironment and PD-L1+ patients with MGUS and asymptomatic MM tend to show disease progression. PD-L1 expression on myeloma cells was associated with more proliferative potential and resistance to antimyeloma agents because of activation of the Akt pathway through PD-1-bound PD-L1 in MM cells. Those data suggest that PD-L1 plays a crucial role in the disease progression of MM. Full article
(This article belongs to the Special Issue The Asymptomatic Version of Myeloma: MGUS and Smoldering Myeloma)
Show Figures

Figure 1

Open AccessReview
Imaging of Monoclonal Gammapathy of Undetermined Significance and Smoldering Multiple Myeloma
Cancers 2020, 12(2), 486; https://doi.org/10.3390/cancers12020486 - 19 Feb 2020
Abstract
Multiple myeloma (MM) is always preceded by an initial monoclonal gammopathy of undetermined significance (MGUS) that then develops into asymptomatic or smoldering multiple myeloma (SMM), which constitutes an intermediate clinical stage between MGUS and MM. According to a recent study, risk factors for [...] Read more.
Multiple myeloma (MM) is always preceded by an initial monoclonal gammopathy of undetermined significance (MGUS) that then develops into asymptomatic or smoldering multiple myeloma (SMM), which constitutes an intermediate clinical stage between MGUS and MM. According to a recent study, risk factors for faster MGUS to MM progression include an M protein of 1.5 g/dL or more and an abnormal free light chain ratio in patients with non-IgM MGUS. Therefore, the International Myeloma Working Group (IMWG) decided to recommend whole-body computed tomography (WBCT) for patients with high-risk MGUS in order to exclude early bone destruction. Studies evaluating magnetic resonance imaging (MRI) in SMM found an optimal cutoff of two or more focal lesions to be of prognostic significance for fast progression into symptomatic disease and considered this biomarker as a myeloma-defining event (MDE) needing to start therapy with the aim to avoid progression to harmful bone lesions. Moreover, studies assessing positron emission tomography (PET) with computed tomography (CT) using 18F-deoxyglucose (FDG) (FDG-PET/CT) in SMM showed that presence of focal bone lesion without underlying osteolysis is associated with a rapid progression to symptomatic MM. Latest IMWG guidelines recommended to perform WBCT (either CT alone or as part of an FDG-PET/CT protocol) as the first imaging technique at suspected SMM and, if these images are negative or inconclusive, to perform whole-body MRI. The goal of this paper is to clarify the role of different imaging modalities in MGUS and SMM workups. Full article
(This article belongs to the Special Issue The Asymptomatic Version of Myeloma: MGUS and Smoldering Myeloma)
Show Figures

Figure 1

Back to TopTop