Assessment of Discordance Among Smoldering Multiple Myeloma Risk Models.
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ABSTRACT:
SUBMITTER: Hill E
PROVIDER: S-EPMC7677870 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Smoldering myeloma is an asymptomatic plasma cell dyscrasia with a heterogeneous propensity to progress to active myeloma. In order to investigate the biology of smoldering myeloma patients with high risk of progression, we analyzed the genomic characteristics by FISH, SNP-arrays and gene expression profile of a group of patients with high-risk smoldering myeloma included in a multicenter randomized trial. Chromosomal abnormalities detected by FISH and SNP-arrays at diagnosis were not associated to risk of progression to symptomatic myeloma. However, the overexpression of four SNORD genes (SNORD25, SNORD27, SNORD30 and SNORD31) was correlated with shorter time to progression (P<0.03). When plasma cells from high-risk smoldering patients who progressed to symptomatic myeloma were sequentially analyzed, newly acquired lesions together with an increase in the proportion of plasma cells carrying a given abnormality were observed. These findings suggest that gene expression profiling is a valuable technique to identify smoldering myeloma patients with high risk of progression. (Clinical Trials NCT00443235).
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Project description:Multiple myeloma, a bone marrow cancer, is preceded by precursor stages called monoclonal gammopathy of unknown significance and smoldering multiple myeloma. Over the past few years, highly effective and safe therapies have been made available to treat multiple myeloma. This represents a major breakthrough and has major therapeutic implications. Treatment for multiple myeloma has evolved to include treatment of precursor stages (early treatment) as these therapies are shown to be safe and effective also in smoldering myeloma. Randomized studies have shown that early treatment can delay the onset of multiple myeloma and even improve overall survival compared to observation in smoldering myeloma. The best therapeutic course and selection of patients with smoldering myeloma to treat is still a matter of debate. In this manuscript, we review the definition, management, clinical implications of smoldering myeloma and early detection of myeloma in the current context and with up-to-date data.
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Project description:Novel therapies hold promise for high-risk smoldering multiple myeloma (SMM). Recent studies suggest that modern combination approaches can be options for high-risk SMM to obtain deep molecular responses with favorable toxicity profiles. Although pioneering treatment trials based on small numbers of patients suggest progression-free and overall survival benefits, application of the data to real-life practice remains to be validated. Therapeutic modulation of disease tempo, disease burden, clonal evolution, and tumor microenvironment in SMM remains to be understood and calls for reliable biomarkers reflective of disease biology. Here, we review studies that open a new management platform for SMM, address ongoing dilemmas in practice and under investigation, and highlight emerging scientific questions in the era of SMM treatment.
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Project description:The adage for smoldering myeloma (SMM) has been to observe without treatment, until criteria for active multiple myeloma were satisfied. Definitions and risk stratification models have become more sophisticated, with prognostication tailored to include high-risk cytogenetics as per the most recent International Myeloma Working Group 2020 risk model. Moreover, progress in defining genomic evolution and changes in the bone marrow microenvironment through the monoclonal continuum have given insight into the complexities underlying the different patterns of progression observed in SMM. Given recent data showing improved progression-free survival with early intervention in high-risk SMM, the current dilemma is focused on how these patients should be treated. This case-based article maps the significant advancements made in the diagnosis and risk stratification of SMM. Data from landmark clinical trials will also be discussed, and ongoing trials are summarized. Ultimately, we outline our approach to SMM and hope to impart to the reader a sound concept of the current clinical management of SMM.
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