Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: biological insights and early treatment strategies

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 478-487 ◽  
Author(s):  
Ola Landgren
Keyword(s):  
Multiple Myeloma ◽  
Patient Outcomes ◽  
Early Treatment ◽  
Monoclonal Gammopathy ◽  
Treatment Strategies ◽  
Precursor State ◽  
The Past ◽  
Smoldering Multiple Myeloma ◽  
Remarkable Progress ◽  
Undetermined Significance

Abstract After decades of virtually no progress, multiple myeloma survival has improved significantly in the past 10 years. Indeed, multiple myeloma has perhaps seen more remarkable progress in treatment and patient outcomes than any other cancer during the last decade. Recent data show that multiple myeloma is consistently preceded by a precursor state (monoclonal gammopathy of undetermined significance [MGUS]/smoldering multiple myeloma [SMM]). This observation provides a framework for prospective studies focusing on transformation from precursor disease to multiple myeloma and for the development of treatment strategies targeting “early myeloma.” This review discusses current biological insights in MGUS/SMM, provides an update on clinical management, and discusses how the integration of novel biological markers, molecular imaging, and clinical monitoring of MGUS/SMM could facilitate the development of early treatment strategies for high-risk SMM (early myeloma) patients in the future.

scholarly journals Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies

Blood ◽  
2011 ◽  
Vol 117 (21) ◽  
pp. 5573-5581 ◽  
Author(s):  
Neha Korde ◽  
Sigurdur Y. Kristinsson ◽  
Ola Landgren
Keyword(s):  
Multiple Myeloma ◽  
Early Treatment ◽  
Monoclonal Gammopathy ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Current Standard ◽  
Smoldering Multiple Myeloma ◽  
Molecular Events ◽  
Unknown Significance ◽  
Risk Of Progression

Abstract Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed.

scholarly journals Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
Sæmundur Rögnvaldsson ◽  
Thorvardur Jon Love ◽  
Sigrun Thorsteinsdottir ◽  
Elín Ruth Reed ◽  
Jón Þórir Óskarsson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Early Treatment ◽  
Monoclonal Gammopathy ◽  
Controlled Trial ◽  
Participation Rate ◽  
Population Based ◽  
Early Therapy ◽  
Screening Study ◽  
Undetermined Significance

AbstractMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.

Prognostic Factors for Malignant Transformation in Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma

2002 ◽  
Vol 20 (6) ◽  
pp. 1625-1634 ◽  
Author(s):  
Clara Cesana ◽  
Catherine Klersy ◽  
Luciana Barbarano ◽  
Anna Maria Nosari ◽  
Monica Crugnola ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Extramedullary Plasmacytoma ◽  
Lymphocytic Leukemia ◽  
Cumulative Probability ◽  
Primary Amyloidosis ◽  
Smoldering Multiple Myeloma ◽  
Bence Jones Proteinuria ◽  
Undetermined Significance

PURPOSE: To evaluate the natural history of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), identify early predictors of evolution, and assess whether associated conditions correlate with disease progression. PATIENTS AND METHODS: A total of 1,231 consecutive patients with either MGUS (n = 1,104) or SMM (n = 127) diagnosed from July 1975 to March 1998 were included in the study. Cumulative survival probability and cumulative probability of transformation into lymphoproliferative disease were calculated by means of the Kaplan-Meier estimator. Univariate and multivariate Cox models were used to identify possible predictors of malignant evolution. RESULTS: Cumulative transformation probability at 10 and 15 years was 14% and 30%, respectively. At a median follow-up of 65 months (range, 12 to 239 months), 64 MGUS cases (5.8%) evolved to multiple myeloma (MM) (n = 43), extramedullary plasmacytoma (n = 1), primary amyloidosis (n = 1), Waldenström’s macroglobulinemia (n = 12), non-Hodgkin’s lymphoma (n = 6), and B-chronic lymphocytic leukemia (n = 1). At a median follow-up of 72 months (range, 12 to 247 months), 25 SMMs (19.7%) evolved to overt MM. A lower evolution risk was observed in MGUS than in SMM (P < .0001). Greater than 5% marrow plasmacytosis, detectable Bence Jones proteinuria, polyclonal serum immunoglobulin reduction, and high erythrocyte sedimentation rate (ESR) were independent factors influencing MGUS transformation. SMM progression correlated with greater than 10% marrow plasma cells, detectable Bence Jones proteinuria, and immunoglobulin (Ig) A isotype. Neither concomitant diseases nor immunosuppression correlated with progression. CONCLUSION: Careful evaluation of marrow plasmacytosis, urinary paraprotein, background immunoglobulins, ESR, and paraprotein isotype might help identify at presentation patients with benign monoclonal gammopathies requiring stricter monitoring.

scholarly journals Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma

Blood Reviews ◽  
2007 ◽  
Vol 21 (5) ◽  
pp. 255-265 ◽  
Author(s):  
S. Vincent Rajkumar ◽  
Martha Q. Lacy ◽  
Robert A. Kyle
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Smoldering Multiple Myeloma ◽  
Undetermined Significance

Progression risk for MGUS and SMM

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2226-2226 ◽  
Author(s):  
Philip Greipp
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Smoldering Multiple Myeloma ◽  
Risk Of Progression ◽  
Progression Risk ◽  
Undetermined Significance

Patients with monoclonal gammopathy of undetermined significance (MGUS) are at continuous risk of progression. Each year, 1% progress, usually to active multiple myeloma (MM).1 Such patients must be monitored for life. Asymptomatic smoldering multiple myeloma (SMM) has an even greater risk of progression to MM. Recently reported strategies improve our ability to estimate the risk of MM in these patients.

scholarly journals Familial monoclonal gammopathy of undetermined significance and multiple myeloma: epidemiology, risk factors, and biological characteristics

Blood ◽  
2012 ◽  
Vol 119 (23) ◽  
pp. 5359-5366 ◽  
Author(s):  
Alexandra J. Greenberg ◽  
S. Vincent Rajkumar ◽  
Celine M. Vachon
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
General Population ◽  
Monoclonal Gammopathy ◽  
Lymphoproliferative Disorders ◽  
Genetic Influences ◽  
Future Directions ◽  
The Past ◽  
Undetermined Significance ◽  
Premalignant Conditions

Abstract Monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma (MM), is one of the most common premalignant conditions in the general population. The cause of MGUS is largely unknown. Recent studies show that there is an increased prevalence of MGUS in blood relatives of persons with lymphoproliferative and plasma cell proliferative disorders, suggesting presence of shared underlying genetic influences. In the past few years, additional studies have examined risk factors and biologic characteristics that may contribute to the increased prevalence of MGUS among relatives of probands with MGUS, MM, and other blood malignancies. This article reviews the known epidemiology and risk factors for familial MGUS and myeloma, the risk of lymphoproliferative disorders and other malignancies among blood-relatives of patients with MGUS and MM, and discusses future directions for research.

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