Management of Newly Diagnosed Symptomatic Multiple Myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines

Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Mayo Clinic Proceedings (Impact Factor: 6.26). 12/2009; 84(12):1095-110. DOI: 10.4065/mcp.2009.0603
Source: PubMed


Multiple myeloma is a malignant plasma cell neoplasm that affects more than 20,000 people each year and is the second most common hematologic malignancy. It is part of a spectrum of monoclonal plasma cell disorders, many of which do not require active therapy. During the past decade, considerable progress has been made in our understanding of the disease process and factors that influence outcome, along with development of new drugs that are highly effective in controlling the disease and prolonging survival without compromising quality of life. Identification of well-defined and reproducible prognostic factors and introduction of new therapies with unique modes of action and impact on disease outcome have for the first time opened up the opportunity to develop risk-adapted strategies for managing this disease. Although these risk-adapted strategies have not been prospectively validated, enough evidence can be gathered from existing randomized trials, subgroup analyses, and retrospective studies to develop a working framework. This set of recommendations represents such an effort-the development of a set of consensus guidelines by a group of experts to manage patients with newly diagnosed disease based on an interpretation of the best available evidence.

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Available from: Shaji K Kumar, Dec 12, 2014
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    • "To determine the selected genes and categories to compile the RAG model, the evidence from studies linking genetic aberrations to prognosis/risk was reviewed. The criteria used to evaluate the evidence was based on established methods used by other groups and is represented in Table 6 [28]. For a gene to have been selected, it must have been independently supported by grade A recommendation, with those aberrations linked to a poor prognosis being placed into the red group, those linked to superior survival placed into the green group, and those of a neutral prognostic impact placed into the amber group. "
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    ABSTRACT: Molecular studies have shown that multiple myeloma is a highly genetically heterogonous disease which may manifest itself as any number of diverse subtypes each with variable clinicopathological features and outcomes. Given this genetic heterogeneity, a universal approach to treatment of myeloma is unlikely to be successful for all patients and instead we should strive for the goal of personalised therapy using rationally informed targeted strategies. Current DNA sequencing technologies allow for whole genome and exome analysis of patient myeloma samples that yield vast amounts of genetic data and provide a mutational overview of the disease. However, the clinical utility of this information currently lags far behind the sequencing technology which is increasingly being incorporated into clinical practice. This paper attempts to address this shortcoming by proposing a novel genetically based "traffic-light" risk stratification system for myeloma, termed the RAG (Red, Amber, Green) model, which represents a simplified concept of how complex genetic data may be compressed into an aggregate risk score. The model aims to incorporate all known clinically important trisomies, translocations, and mutations in myeloma and utilise these to produce a score between 1.0 and 3.0 that can be incorporated into diagnostic, prognostic, and treatment algorithms for the patient.
    Full-text · Article · Sep 2014
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    • "Przykładowo, najbardziej złożona wydaje się omawiana powyżej klasyfikacja mSMART, którą opracowano na podstawie analizy wartości prognostycznej anomalii chromosomowych oraz wybranych negatywnie rokujących czynników biochemicznych, morfologicznych lub molekularnych [18]. Pierwotnie model przewidywał dwie kategorie rokownicze: grupę standardowego ryzyka (około 75% chorych) oraz grupę wysokiego ryzyka (25% chorych) [31] [32]. Ostatnio klasyfikacja ta została poszerzona o trzecią kategorię ryzyka pośredniego, obejmującą przede wszystkim pacjentów z t(4;14). "
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    ABSTRACT: A remarkable progress, which has been made during the last two decades in the multiple myeloma (MM) treatment, is mainly associated with the introduction to MM therapy three new drugs - thalidomide, lenalidomide and bortezomib. Global improvement of prognosis in MM, confirmed by numerous clinical trials and epidemiological studies, is mainly a consequence of very favorable results obtained in patients in the standard-risk group. However, in patients affected by prognostically unfavorable chromosomal aberrations, who constitute approximately 25% of all MM patients, only a slight improvement in the prognosis has become possible. Interestingly, the effectiveness of various new drugs for patients in the high-risk group appears to be different. The results of clinical trials indicate that currently bortezomib seems to be the most effective drug for patients with unfavorable cytogenetic abnormalities, especially patients with translocation t(4;14). In the present article the published data on the efficacy of bortezomib in first-line therapy in patients with unfavorable cytogenetic abnormalities are reviewed. The principles of risk stratification and individualization of therapy in MM are also discussed.
    Preview · Article · Jul 2014 · Acta haematologica Polonica
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    • "Although the limited number of patients in this study restricted the clarification of the prognostic significance, t(11;14) was associated with higher albumin levels, which may be related to mild clinical manifestation. t(4;14) was more frequently found in old patients, and it was associated with del(13q) that was detected with conventional cytogenetics and that is a well-known intermediate risk factor [23]. "
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    ABSTRACT: We reviewed patients with multiple myeloma (MM) in order to assess the incidence of genetic abnormalities and their associations with clinical parameters, risk groups, and prognosis. A total of 130 patients with MM were enrolled. The incidences of genetic abnormalities were determined in all patients. The relationships of the genetic abnormalities and clinical parameters were investigated. In addition, a survival analysis was performed. Abnormal karyotypes were detected in 42.3% (N=55) of the patients, and this was increased to 63.1% (N=82) after including the results determined with interphase FISH. Hypodiploidy was observed in 7.7% (N=10) of the patients, and all were included in the group with complex karyotypes (30.8%, N=40). The 14q32 rearrangements were detected in 29.2% (N=38) of the patients, and these most commonly included t(11;14), which was followed by t(4;14) and t(14;16) (16.2%, 11.5%, and 0.8%, respectively). Abnormal karyotypes and complex karyotypes were associated with disease progression markers, including low hemoglobin levels, low platelet counts, high plasma cell burden, high β2-microglobulin, and high international staging system stages. A high free light chain (FLC) ratio and FLC difference were associated with abnormal karyotypes, complex karyotypes, and higher plasma cell burden. Hypodiploidy and low platelet counts were significant independent prognostic factors and were more important in patient outcome than any single abnormality. Genetic abnormalities were associated with disease progression markers and prognosis of MM patients.
    Full-text · Article · Jul 2013 · Annals of Laboratory Medicine
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