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Gammopathies of Certain Significance: Managing MGUS and Smoldering Myeloma

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

Deadline for manuscript submissions: closed (1 September 2022) | Viewed by 12260

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Special Issue Editors

Dr. Maximilian Merz

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Guest Editor

1. Department of Hematology, Oncology and Rheumatology, University Hospital of Heidelberg, 69120 Heidelberg, Germany
2. Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, New York, USA
Interests: Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance; Smoldering Myeloma; Autologous Stem Cell Transplantation; MRI; PET/CT; Genetics; Clinical Trials

Prof. Dr. Hartmut Goldschmidt

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Guest Editor

1. Department of Hematology, Oncology and Rheumatology, University Hospital of Heidelberg, 69120 Heidelberg, Germany
2. National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
Interests: Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance; Smoldering Myeloma; Autologous Stem Cell Transplantation; MRI; PET/CT; Genetics; Clinical Trials; CAR T-Cells; Immunotherapy

Special Issue Information

Dear Colleagues,

Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM) consistently precede symptomatic Multiple Myeloma (MM) requiring systemic treatment. During the last decade, tremendous efforts have been made to understand the biological backgrounds for disease progression which changed the clinical management of patients with MGUS and SMM. The introduction of the Slim-CRAB criteria by the International Myeloma Working Group (IMWG) in 2014 and the first clinical trials on treatment of high-risk SMM published in 2013 and 2019 were significant milestones that changed the treatment paradigm for patients with asymptomatic plasma cell disorders. Recently, the IMWG introduced the new 20/2/20 stratification system to identify high-risk SMM patients, who do not meet Slim-CRAB criteria but should be monitored closely for disease progression. Furthermore, a second generation of clinical trials in high-risk SMM patients is on its way, not only aiming at prolonging time-to-progression but ultimately curing the disease at a stage where it is not characterized by significant clonal heterogeneity that occurs during progression.

Besides the changes in the management of high-risk SMM, there is also an increasing awareness for MGUS-associated conditions requiring special attention, like light-chain amyloidosis, neuropathies caused by paraproteins, Monoclonal Gammopathy of Renal Significance (MGRS) as well as POEMS and CANOMAD syndrome.

This special issue entitled Gammopathies of Certain Significance: Managing MGUS and Smoldering Myeloma represents are collaborative effort to highlight the current standard of care and future developments in the clinical care of patients with MM precursor diseases.

Dr. Maximilian Merz
Prof. Dr. Hartmut Goldschmidt
Guest Editors

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 submissions that pass pre-check are 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.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 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 of Undetermined Significance
Smoldering Multiple Myeloma
Magnetic Resonance Imaging
PET/CT
Clinical Trials
Monoclonal Gammopathy of Renal Significance

Published Papers (5 papers)

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Research

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15 pages, 2049 KiB

Open AccessArticle

Prognostic Relevance of Multi-Antigenic Myeloma-Specific T-Cell Assay in Patients with Monoclonal Gammopathies

by Ivana Lagreca, Vincenzo Nasillo, Patrizia Barozzi, Ilaria Castelli, Sabrina Basso, Sara Castellano, Ambra Paolini, Monica Maccaferri, Elisabetta Colaci, Daniela Vallerini, Patrizia Natali, Daria Debbia, Tommaso Pirotti, Anna Maria Ottomano, Rossana Maffei, Francesca Bettelli, Davide Giusti, Andrea Messerotti, Andrea Gilioli, Valeria Pioli, Giovanna Leonardi, Fabio Forghieri, Paola Bresciani, Angela Cuoghi, Monica Morselli, Rossella Manfredini, Giuseppe Longo, Anna Candoni, Roberto Marasca, Leonardo Potenza, Enrico Tagliafico, Tommaso Trenti, Patrizia Comoli, Mario Luppi and Giovanni Riva Show full author list Hide full author list

Cancers 2023, 15(3), 972; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15030972 - 03 Feb 2023

Cited by 1 | Viewed by 1748

Abstract

Multiple Myeloma (MM) typically originates from underlying precursor conditions, known as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). Validated risk factors, related to the main features of the clonal plasma cells, are employed in the current prognostic models to assess long-term probabilities of progression to MM. In addition, new prognostic immunologic parameters, measuring protective MM-specific T-cell responses, could help to identify patients with shorter time-to-progression. In this report, we described a novel Multi-antigenic Myeloma-specific (MaMs) T-cell assay, based on ELISpot technology, providing simultaneous evaluation of T-cell responses towards ten different MM-associated antigens. When performed during long-term follow-up (mean 28 months) of 33 patients with either MGUS or SMM, such deca-antigenic myeloma-specific immunoassay allowed to significantly distinguish between stable vs. progressive disease (p < 0.001), independently from the Mayo Clinic risk category. Here, we report the first clinical experience showing that a wide (multi-antigen), standardized (irrespective to patients’ HLA), MM-specific T-cell assay may routinely be applied, as a promising prognostic tool, during the follow-up of MGUS/SMM patients. Larger studies are needed to improve the antigenic panel and further explore the prognostic value of MaMs test in the risk assessment of patients with monoclonal gammopathies. Full article

(This article belongs to the Special Issue Gammopathies of Certain Significance: Managing MGUS and Smoldering Myeloma)

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19 pages, 1262 KiB

Open AccessArticle

Accuracy and Reliability of Internet Resources for Information on Monoclonal Gammopathy of Undetermined Significance—What Information Is out There for Our Patients?

by Emma Pauline Kreutzer, Sandra Sauer, Mark Kriegsmann, Henrike Staemmler, Gerlinde Egerer and Katharina Kriegsmann

Cancers 2021, 13(18), 4508; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13184508 - 07 Sep 2021

Cited by 3 | Viewed by 1606

Abstract

Background: Online information gathering can increase patients’ engagement in decision-making. The quality of online resources available for monoclonal gammopathy of undetermined significance (MGUS) was evaluated. Methods: 900 websites from Google, Bing, Yahoo, and 150 YouTube videos were assessed. Results: The websites did not differ regarding their search rank or between the search engines. The median time since last update was 24 months. The 86 unique websites showed a medium to poor general quality (JAMA score 3/4, only 8.1% websites with a valid HON certificate). The patient- (user-) focused quality was poor (sum DISCERN score 27/80 points). The reading level was difficult (11th US school grade). The content level was very low (13/50 points). 12.8% of websites contained misleading/wrong facts. Websites provided by scientific/governmental organizations had a higher content level. For the 61 unique videos, the median time since upload was 34 months. The videos showed a medium general quality (HON Foundation score). The patient- (user-) focused quality was poor (sum DISCERN score 24 points). The content level was very low (6 points). Conclusion: MGUS-relevant online sources showed a low quality that was provided on a high reading level. Incorporation of quality indices and regular review of online content is warranted. Full article

(This article belongs to the Special Issue Gammopathies of Certain Significance: Managing MGUS and Smoldering Myeloma)

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12 pages, 2411 KiB

Open AccessArticle

Pathogenetic and Prognostic Implications of Increased Mitochondrial Content in Multiple Myeloma

by Yanira Ruiz-Heredia, Alejandra Ortiz-Ruiz, Mehmet K. Samur, Vanesa Garrido, Laura Rufian, Ricardo Sanchez, Pedro Aguilar-Garrido, Santiago Barrio, Miguel A. Martín, Niccolò Bolli, Yu-Tzu Tai, Raphaël Szalat, Mariateresa Fulciniti, Nikhil Munshi, Joaquín Martínez-López, María Linares and Miguel Gallardo

Cancers 2021, 13(13), 3189; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13133189 - 25 Jun 2021

Cited by 3 | Viewed by 2469

Abstract

Many studies over the last 20 years have investigated the role of mitochondrial DNA (mtDNA) alterations in carcinogenesis. However, the status of the mtDNACN in MM and its implication in the pathogenesis of the disease remains unclear. We examined changes in plasma cell mtDNACN across different stages of MM by applying RT-PCR and high-throughput sequencing analysis. We observed a significant increase in the average mtDNACN in myeloma cells compared with healthy plasma cells (157 vs. 40 copies; p = 0.02). We also found an increase in mtDNACN in SMM and newly diagnosed MM (NDMM) paired samples and in consecutive relapses in the same patient. Survival analysis revealed the negative impact of a high mtDNACN in progression-free survival in NDMM (p = 0.005). Additionally, we confirmed the higher expression of mitochondrial biogenesis regulator genes in myeloma cells than in healthy plasma cells and we detected single nucleotide variants in several genes involved in mtDNA replication. Finally, we found that there was molecular similarity between “rapidly-progressing SMM” and MM regarding mtDNACN. Our data provide evidence that malignant transformation of myeloma cells involves the activation of mitochondrial biogenesis, resulting in increased mtDNA levels, and highlights vulnerabilities and potential therapeutic targets in the treatment of MM. Accordingly, mtDNACN tracking might guide clinical decision-making and management of complex entities such as high-risk SMM. Full article

(This article belongs to the Special Issue Gammopathies of Certain Significance: Managing MGUS and Smoldering Myeloma)

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15 pages, 5071 KiB

Open AccessArticle

Analyzing Longitudinal wb-MRI Data and Clinical Course in a Cohort of Former Smoldering Multiple Myeloma Patients: Connections between MRI Findings and Clinical Progression Patterns

by Markus Wennmann, Thomas Hielscher, Laurent Kintzelé, Bjoern H. Menze, Georg Langs, Maximilian Merz, Sandra Sauer, Hans-Ulrich Kauczor, Heinz-Peter Schlemmer, Stefan Delorme, Hartmut Goldschmidt, Niels Weinhold, Jens Hillengass and Marc-André Weber

Cancers 2021, 13(5), 961; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13050961 - 25 Feb 2021

Cited by 8 | Viewed by 1900

Abstract

The purpose of this study was to analyze size and growth dynamics of focal lesions (FL) as well as to quantify diffuse infiltration (DI) in untreated smoldering multiple myeloma (SMM) patients and correlate those MRI features with timepoint and cause of progression. We investigated 199 whole-body magnetic resonance imaging (wb-MRI) scans originating from longitudinal imaging of 60 SMM patients and 39 computed tomography (CT) scans for corresponding osteolytic lesions (OL) in 17 patients. All FLs >5 mm were manually segmented to quantify volume and growth dynamics, and DI was scored, rating four compartments separately in T1- and fat-saturated T2-weighted images. The majority of patients with at least two FLs showed substantial spatial heterogeneity in growth dynamics. The volume of the largest FL (p = 0.001, c-index 0.72), the speed of growth of the fastest growing FL (p = 0.003, c-index 0.75), the DI score (DIS, p = 0.014, c-index 0.67), and its dynamic over time (DIS dynamic, p < 0.001, c-index 0.67) all significantly correlated with the time to progression. Size and growth dynamics of FLs correlated significantly with presence/appearance of OL in CT within 2 years after the respective MRI assessment (p = 0.016 and p = 0.022). DIS correlated with decrease of hemoglobin (p < 0.001). In conclusion, size and growth dynamics of FLs correlate with prognosis and local bone destruction. Connections between MRI findings and progression patterns (fast growing FL—OL; DIS—hemoglobin decrease) might enable more precise diagnostic and therapeutic approaches for SMM patients in the future. Full article

(This article belongs to the Special Issue Gammopathies of Certain Significance: Managing MGUS and Smoldering Myeloma)

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Review

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16 pages, 10539 KiB

Open AccessReview

From Biology to Treatment of Monoclonal Gammopathies of Neurological Significance

by Andrea Visentin, Stefano Pravato, Francesca Castellani, Marta Campagnolo, Francesco Angotzi, Chiara Adele Cavarretta, Alessandro Cellini, Valeria Ruocco, Alessandro Salvalaggio, Alessandra Tedeschi, Livio Trentin and Chiara Briani

Cancers 2022, 14(6), 1562; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14061562 - 18 Mar 2022

Cited by 8 | Viewed by 3413

Abstract

Monoclonal gammopathy and peripheral neuropathy are common diseases of elderly patients, and almost 10% of patients with neuropathy of unknown cause have paraprotein. However, growing evidence suggests that several hematological malignancies synthesize and release monoclonal proteins that damage the peripheral nervous system through different mechanisms. The spectrum of the disease varies from mild to rapidly progressive symptoms, sometimes affecting not only sensory nerve fibers, but also motor and autonomic fibers. Therefore, a multidisciplinary approach, mainly between hematologists and neurologists, is recommended in order to establish the correct diagnosis of monoclonal gammopathy of neurological significance and to tailor therapy based on specific genetic mutations. In this review, we summarize the spectrum of monoclonal gammopathies of neurological significance, their distinctive clinical and neurophysiological phenotypes, the most relevant pathophysiological events and new therapeutic approaches. Full article

(This article belongs to the Special Issue Gammopathies of Certain Significance: Managing MGUS and Smoldering Myeloma)

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