Smoldering multiple myeloma: Reviewing the rationale for intervention

Gertz, Morie A.

doi:10.1080/10428194.2022.2068008

Cited by 3 publications

(1 citation statement)

References 41 publications

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“…In clinical practice, three models are used to predict the progression of MGUS and SMM to MM: the Mayo Clinic, the Spanish Study group, and the IWMG 20/2/20 risk stratification systems [ 3 , 4 , 5 ]. These models include parameters of higher disease burden, such as a higher monoclonal protein level, a higher free light chain (FLC) ratio, and a greater percentage of monoclonal PCs in bone marrow (BM).…”

Section: Introductionmentioning

confidence: 99%

The Involvement of LAG-3positive Plasma Cells in the Development of Multiple Myeloma

Kreiniz,

Eiza,

Tadmor

et al. 2023

IJMS

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The Lymphocyte-Activation Protein 3 (LAG-3) inhibitory receptor is expressed on regulatory plasma cells (PCs). Micro-environmental cells that express LAG-3 were found to be increased during the progression of smoldering multiple myeloma (SMM). To assess the possible role of LAG-3 expression on regulatory PCs in patients with plasma cell dyscrasia. Purified Cluster of Differentiation 138 (CD138+) PCs from patients with premalignant conditions, active multiple myeloma (MM), and controls were analyzed for the expression of LAG-3 by flow cytometry. Autologous CD8+T cells were incubated with sorted LAG-3pos or LAG-3neg PCs for 24 h. The expression of granzyme (Grz) in CD8+T cells was assessed by flow cytometry. LAG-3 expression on PCs in active MM (newly diagnosed and relapse refractory MM) was significantly increased compared to monoclonal gammopathy of undetermined significance (MGUS)/ SMM. Grz expression was significantly decreased in CD8+T cells incubated with CD138+LAG-3pos PCs, compared to CD138+LAG-3neg PCs in patients with plasma cell dyscrasia, n = 31, p = 0.0041. LAG-3 expression on malignant PCs can be involved in the development of MM from MGUS by decreasing the expression of Grz in CD8+T cells.

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Section: Introductionmentioning

confidence: 99%

The Involvement of LAG-3positive Plasma Cells in the Development of Multiple Myeloma

Kreiniz,

Eiza,

Tadmor

et al. 2023

IJMS

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Screening in Multiple Myeloma and Its Precursors: Are We There Yet?

Rögnvaldsson,

Thorsteinsdóttir,

Kristinsson

2024

Clinical Chemistry

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Background Multiple myeloma (MM) is a hematological malignancy that develops over years from the asymptomatic precursors, monoclonal gammopathy of undetermined significance, and smoldering multiple myeloma. Recent evidence shows that by initiating treatment at an asymptomatic stage, outcomes in MM can be significantly improved. However, a vast majority of MM patients are diagnosed after the development of symptomatic end-organ damage and cannot reap the benefits of early treatment. The precursors of MM are easily detected by serum protein electrophoresis and free light chain assay of the serum, raising the question of whether population-based screening could detect MM at an asymptomatic stage and significantly expand the availability of early treatment in MM. Screening is a hallmark of care in many malignancies, and there are accepted criteria for when screening is appropriate. Content Here we review the available relevant evidence for the introduction of screening and discuss whether screening for MM and its precursors fulfills these criteria. We also highlight gaps in our current knowledge, most notably a lack of data on the benefits and harms of screening and the lack of a defined target population. There are ongoing studies that may fill these critical gaps in the literature, but their results are still pending. Summary Screening could lead to a paradigm shift in the care of patients with MM, but critical scientific questions need to be answered before screening of healthy individuals can be recommended. In short, we should not screen for MM and its precursors—yet.

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A blueprint for pursuing therapeutic interventions and early phase clinical trials in clonal haematopoiesis

Haque,

Shastri,

Desai

et al. 2024

Br J Haematol

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SummaryThe age‐associated mutational state of clonal haematopoiesis (CH) is linked to multiple adverse health outcomes. As higher risk CH can lead to progressive neoplastic or vascular disease, there is interest in developing clinical trials to mitigate risk associated with CH. Given the high prevalence of CH, data from clinical trials could have broad public health implications for screening and therapy. Thoughtful consideration is needed to design trials that are both clinically relevant and avoid overmedicalization. Here, we summarize clinical studies of CH to date and provide suggestions and guidance on how to approach designing CH‐focused therapeutic clinical trials. These recommendations are derived from discussions among clinical researchers and scientists emanating from the Inaugural Meeting on Somatic Mutations and Predisease in October 2021.

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Smoldering multiple myeloma: Reviewing the rationale for intervention

Cited by 3 publications

References 41 publications

The Involvement of LAG-3positive Plasma Cells in the Development of Multiple Myeloma

The Involvement of LAG-3positive Plasma Cells in the Development of Multiple Myeloma

Screening in Multiple Myeloma and Its Precursors: Are We There Yet?

A blueprint for pursuing therapeutic interventions and early phase clinical trials in clonal haematopoiesis

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