A first Czech analysis of 1887 cases with monoclonal gammopathy of undetermined significance

Sandecká, Viera; Hájek, Roman; Pour, Luděk; Špıčka, Ivan; Scudla, Vlastimil; Gregora, Evžen; Radocha, Jakub; Walterova, Lenka; Kessler, Petr; Zahradová, Lenka; Adamová, D.; Valentova, Kamila; Vonke, Ivan; Obernauerová, Jarmila; Starostka, David; Wróbel, Marek; Brožová, Lucie; Jarkovský, Jiří; Mikulášová, Aneta; Říhová, Lucie; Ševčı́ková, Sabina; Štraub, Jan; Minařík, Jiří; Adam, Zdeněk; Krejčí, Marta; Král, Zdeněk; Maisnar, Vladimír

doi:10.1111/ejh.12894

Cited by 8 publications

(10 citation statements)

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“…From this model, based on an analysis of 1384 MGUS patients diagnosed between 1960 and 1994 in Minnesota, USA, the three risk factor, abnormal FLCr, non‐IgG isotype and M‐spike >1.5 g/dL, were identified 5,6 . Recent studies have not been able to confirm the increased risk of progression in non‐IgG (with or without IgM MGUS in the study population) 12,13,21,22 . Similar to these publications, we have not seen a significantly increased risk of progression in the patient population with non‐IgG isotype.…”

Section: Discussionsupporting

confidence: 71%

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Comparative evaluation of involved free light chain and monoclonal spike as markers for progression from monoclonal gammopathy of undetermined significance to multiple myeloma

et al. 2020

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Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal plasma cell disorder, with a 1% yearly risk of progression to multiple myeloma (MM). Evolution of M‐spike and serum free light chain (sFLC) during follow‐up could identify patients at high risk of progression. In this region‐wide study, including 4756 individuals, 987 patients with MGUS were identified, and baseline factors as well as evolving involved FLC (iFLC) were evaluated as potential markers for risk of progression from MGUS to MM. Furthermore, evolving iFLC and M‐spike were assessed quarterly for a median of 5 years. At baseline, patients that progressed had significantly higher iFLC compared to non‐progressors. The risk factors of M‐spike >1.5 g/dL, age >65 years and iFLC >100 mg/L were all independently associated with increased risk of MGUS to MM progression. For patients that had any two or three risk factors, the 5‐year cumulative probability of progression was significantly higher (31%) compared to no risk factors (2%). Evolving iFLC >100 mg/L during follow‐up was consistently associated with increased risk of progression. Based on our observations, we propose to include iFLC as a monitoring tool for all MGUS patients. Furthermore, we recommend a quarterly monitoring in all high‐risk patients. Finally, we suggest that the risk of MGUS progression should be stratified with age, M‐spike, and iFLC at baseline.

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Section: Discussionsupporting

confidence: 71%

“…Abnormal FLCr are detected in more than 95% of MM but only in 30%‐47% of MGUS cases 4,6,11‐13 . It can be hypothesized that evolving sFLC could be a predictor for progression from MGUS to MM.…”

Section: Introductionmentioning

confidence: 99%

Comparative evaluation of involved free light chain and monoclonal spike as markers for progression from monoclonal gammopathy of undetermined significance to multiple myeloma

et al. 2020

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“…MGUS skupina, která měla 4-5 rizikových faktorů, měla 63× vyšší riziko progrese při porovnání s referenční skupinou (p < 0,001), viz tab. 2 [47].…”

Section: Fenotypová Charakteristika Nádorových Plazmatických Buněk a unclassified

Monoclonal Gammopathy of Undetermined Significance (MGUS)

Sandecká¹,

Pour²,

Adam³

et al. 2018

Klin Onkol

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Východiska: Monoklonální gamapatie nejasného významu (monoclonal gammopathy of undetermined significance-MGUS) patří mezi nejčastější premaligní stavy. Riziko maligní transformace je přibližně 1 % za rok. MGUS typu IgG a IgA jsou prekurzory pro mnohočetný myelom (MM), MGUS z lehkých řetězců (light-chain MGUS) pro MM z lehkých řetězců. IgM MGUS je prekurzor pro Morbus Waldenström (MW), nebo jiné lymfoproliferativní onemocnění. Cíl: Klinický průběh pa cientů s asymp tomatickou monoklonální gamapatií (MG) závisí na několika klíčových bio markerech, mezi které patří-koncentrace a typ sérového paraproteinu (M proteinu) v séru, poměr volných lehkých řetězců v séru (free light chain ratio-FLC), infiltrace kostní dřeně plazmocyty, pokles jedného nebo dvou polyklonálních imunoglobulinů (imunoparéza), stabilita koncentrace sérového M proteinu v čase (evolv ing a non-evolv ing typ MGUS), poměr fenotypově normálních a abnormálních populací plazmocytů v kostní dřeni za pomoci flowcytometrické analýzy a přítomnost cirkulujících plazmocytů v periferní krvi. V současné době jsou známy tři rizikově stratifikační modely predikce transformace MGUS do maligní formy monoklonální gamapatie-MAYO, PETHEMA a CMG model. Cílem všech tří modelů je správná identifikace prognostických markerů, na základě kterých lze MGUS pa cienty rozdělit na pa cienty s nízkým rizikem progrese (low-risk MGUS) a vysokým rizikem progrese (high-risk MGUS). Závěr: Tento přehledový článek přináší pohled na definici, patogenezi, dia gnostický algoritmus, klinický význam a stratifikaci pa cientů s MGUS s následným doporučením intervalů dispenzarizací podle rizikovosti pa cienta. Klíčová slova monoklonální gamapatie nejasného významu-mnohočetný myelom-progrese-rizikové faktory Summary Background: Monoclonal gammopathy of undetermined significance (MGUS) is one of the most prevalent premalignant conditions associated with a risk of malignant transformation to multiple myeloma (MM) or other forms of lymphoproliferative disorders with risk of progression of approximately 1% per year. IgG and IgA MGUS are precursor conditions of multiple myeloma (MM), whereas light-chain MGUS is a precursor condition of light chain MM. IgM MGUS is a precursor condition of Waldenström macroglobulinemia (MW) or other lymphoproliferative dis eases. Aim: Assessment of the risk of progression of patients with asymp tomatic monoclonal gammopathies (MG) is based on various factors, includ ing the serum paraprotein (M protein) concentration, isotype of M protein, serum free light chain ratio, infiltration of bone marrow plasmocytes, reduction of one or two noninvolved immunoglobulin subtype levels (immunoparesis), evolv ing and non-evolv ing subtype of MGUS, ratio of normal/ abnormal plasma cells in bone marrow identified by multiparametric flow cytometry techniques and number of circulat ing plasma cells in peripheral blood. Three risk stratification models have been constructed that are useful in daily practice for predict ing risk of progression of MGUS into malignant forms of monoclonal gam...

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“…Immunoparesis with suppression of uninvolved immunoglobulins is a well-recognized feature of multiple myeloma (MM) and has been associated with an inferior prognosis. For example, studies have linked immunoparesis with an increased risk of progression to MM from precursor states (1)(2)(3)(4)(5)(6). Similarly, several studies suggest immunoparesis in newly diagnosed patients is connected with a worse progression-free and overall survival (7,8), while immunoglobulin recovery after high-dose therapy confers a good prognosis (9,10).…”

Section: Introductionmentioning

confidence: 99%

Intravenous Immunoglobulin G Suppresses Heat Shock Protein (HSP)-70 Expression and Enhances the Activity of HSP90 and Proteasome Inhibitors

et al. 2020

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Intravenous immunoglobulin G (IVIgG) is approved for primary immunodeficiency syndromes but may induce anti-cancer effects, and while this has been attributed to its anti-inflammatory properties, IgG against specific tumor targets may play a role. We evaluated IVIgG alone, and with a Heat shock protein (HSP)-90 or proteasome inhibitor, using multiple myeloma and mantle cell lymphoma (MCL) cells in vitro, and with the proteasome inhibitor bortezomib in vivo. IVIgG inhibited the growth of all cell lines tested, induced G 1 cell cycle arrest, and suppressed pro-tumor cytokines including Interleukin (IL)-6, IL-8, and IL-10. Genomic and proteomic studies showed that IVIgG reduced tumor cell HSP70-1 levels by suppressing the ability of extracellular HSP70-1 to stimulate endogenous HSP70-1 promoter activity, and reduced extracellular vesicle uptake. Preparations of IVIgG were found to contain high titers of anti-HSP70-1 IgG, and recombinant HSP70-1 reduced the efficacy of IVIgG to suppress HSP70-1 levels. Combining IVIgG with the HSP90 inhibitor AUY922 produced superior cell growth inhibition and correlated with HSP70-1 suppression. Also, IVIgG with bortezomib or carfilzomib was superior to each single agent, and enhanced bortezomib's activity in bortezomib-resistant myeloma cells. Moreover, IVIgG reduced transfer of extracellular vesicles (EVs) to cells, and blocked transfer of bortezomib resistance through EVs. Finally, IVIgG with bortezomib were superior to the single agents in an in vivo myeloma model. These studies support the possibility that anti-HSP70-1 IgG contained in IVIgG can inhibit myeloma and MCL growth by interfering with a novel mechanism involving uptake of exogenous HSP70-1 which then induces its own promoter.

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A first Czech analysis of 1887 cases with monoclonal gammopathy of undetermined significance

Abstract: The new CMG model was established with an advantage for better identification of MGUS patients at low risk.

Cited by 8 publications

References 21 publications

Comparative evaluation of involved free light chain and monoclonal spike as markers for progression from monoclonal gammopathy of undetermined significance to multiple myeloma

Comparative evaluation of involved free light chain and monoclonal spike as markers for progression from monoclonal gammopathy of undetermined significance to multiple myeloma

Monoclonal Gammopathy of Undetermined Significance (MGUS)

Intravenous Immunoglobulin G Suppresses Heat Shock Protein (HSP)-70 Expression and Enhances the Activity of HSP90 and Proteasome Inhibitors

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