Assessment of Discordance Among Smoldering Multiple Myeloma Risk Models.
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ABSTRACT:
SUBMITTER: Hill E
PROVIDER: S-EPMC7677870 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Assessment of Discordance Among Smoldering Multiple Myeloma Risk Models.
Hill Elizabeth E Dew Alexander A Morrison Candis C Yuan Constance C Stetler-Stevenson Maryalice M Landgren Ola O Kazandjian Dickran D
JAMA oncology 20210101 1
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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:Smoldering multiple myeloma is a heterogeneous asymptomatic precursor to multiple myeloma. Since its identification in 1980, risk stratification models have been developed using two main stratification methods: clinical measurement-based and genetics-based. Clinical measurement models can be subdivided in three types: baseline measurements (performed at diagnosis), evolving measurements (performed over time during follow-up appointments), and imaging (for example, magnetic resonance imaging). Genetic approaches include gene expression profiling, DNA/RNA sequencing, and cytogenetics. It is important to accurately distinguish patients with indolent disease from those with aggressive disease, as clinical trials have shown that patients designated as "high-risk of progression" have improved outcomes when treated early. The risk stratification models, and clinical trials are discussed in this review.
| S-EPMC8750018 | biostudies-literature
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.
| S-EPMC7069728 | biostudies-literature
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.
| S-EPMC4268248 | biostudies-literature
Project description:Smoldering multiple myeloma (SMM) is an asymptomatic condition that occupies a space between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) along the spectrum of clonal plasma cell proliferative disorders. It is not a biologic intermediate stage between MGUS and MM, but rather represents a heterogeneous clinically defined condition in which some patients (approximately two-thirds) have MGUS (pre-malignancy), and some (approximately one-third) have MM (biologic malignancy). Unfortunately, no single pathologic or molecular feature can reliably distinguish these two groups of patients. For purposes of practice and clinical trials, specific risk factors are used to identify patients with SMM in whom malignant transformation has already likely occurred (high risk SMM). Patients with newly diagnosed high risk SMM should be offered therapy with lenalidomide or lenalidomide plus dexamethasone (Rd) for 2 years, or enrollment in clinical trials. Patients with low risk SMM should be observed without therapy every 3-4 months.
| S-EPMC9445066 | biostudies-literature
Project description:The current standard of care in smoldering multiple myeloma (SMM) is close surveillance, outside of clinical trials. Efforts are being made to understand the pathobiologic process that leads to the progression of SMM to active MM. This review provides a critical description of available data, including risk factors and risk models of progression, as well as clinical trials investigating interventions for this patient population. We describe 2 cases in which patients were seen before the concept of a myeloma-defining event was established. Today, based on the International Myeloma Working Group criteria, both patients would have been identified as experiencing myeloma-defining events, and therapy would have been initiated. These cases show that occasionally, patients can undergo observation only, even when they exceed criteria for high-risk SMM.
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Project description:The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.
| S-EPMC7145585 | biostudies-literature
Project description:In 2014, the International Myeloma Working Group reclassified patients with smoldering multiple myeloma (SMM) and bone marrow-plasma cell percentage (BMPC%) ≥ 60%, or serum free light chain ratio (FLCr) ≥ 100 or >1 focal lesion on magnetic resonance imaging as multiple myeloma (MM). Predictors of progression in patients currently classified as SMM are not known. We identified 421 patients with SMM, diagnosed between 2003 and 2015. The median time to progression (TTP) was 57 months (CI, 45-72). BMPC% > 20% [hazard ratio (HR): 2.28 (CI, 1.63-3.20); p < 0.0001]; M-protein > 2g/dL [HR: 1.56 (CI, 1.11-2.20); p = 0.01], and FLCr > 20 [HR: 2.13 (CI, 1.55-2.93); p < 0.0001] independently predicted shorter TTP in multivariate analysis. Age and immunoparesis were not significant. We stratified patients into three groups: low risk (none of the three risk factors; n = 143); intermediate risk (one of the three risk factors; n = 121); and high risk (≥2 of the three risk factors; n = 153). The median TTP for low-, intermediate-, and high-risk groups were 110, 68, and 29 months, respectively (p < 0.0001). BMPC% > 20%, M-protein > 2 g/dL, and FLCr > 20 at diagnosis can be used to risk stratify patients with SMM. Patients with high-risk SMM need close follow-up and are candidates for clinical trials aiming to prevent progression.
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Project description:Smoldering multiple myeloma (SMM) is an asymptomatic precursor condition to multiple myeloma (MM). The prevalence of SMM is 0.5% in persons over 40 years old; it is higher in men than women and increases with age. When SMM is diagnosed, a thorough diagnostic workup is necessary to exclude myeloma-defining events and stratify patients according to risk of progression to MM. While close monitoring for progression remains the best management for most patients with SMM, in this article, we discuss if treatment initiation before myeloma-defining events occur might be relevant in selected high-risk cases. Two randomized clinical trials have shown a clinical benefit of initiating treatment at the SMM stage, whereof 1 showed an overall survival benefit for those receiving treatment. We discuss various risk stratification models in SMM, important treatment trials, and ongoing trials. Finally, we present how to approach the clinical management of patients with SMM.
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