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 Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study

Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5412-5417 ◽  
Author(s):  
Ola Landgren ◽  
Robert A. Kyle ◽  
Ruth M. Pfeiffer ◽  
Jerry A. Katzmann ◽  
Neil E. Caporaso ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Population Based ◽  
Serum Samples ◽  
M Proteins ◽  
Cancer Screening Trial ◽  
Risk Of Progression ◽  
Study Population ◽  
A Prospective Study ◽  
Undetermined Significance

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma-cell proliferative disorder associated with a life-long risk of progression to multiple myeloma (MM). It is not known whether MM is always preceded by a premalignant asymptomatic MGUS stage. Among 77 469 healthy adults enrolled in the nationwide population-based prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 71 subjects who developed MM during the course of the study in whom serially collected (up to 6) prediagnostic serum samples obtained 2 to 9.8 years prior to MM diagnosis were available. Using assays for monoclonal (M)–proteins (electrophoresis/immunofixation) and kappa-lambda free light chains (FLCs), we determined longitudinally the prevalence of MGUS and characterized patterns of monoclonal immunoglobulin abnormalities prior to MM diagnosis. MGUS was present in 100.0% (87.2%-100.0%), 98.3% (90.8%-100.0%), 97.9% (88.9%-100.0%), 94.6% (81.8%-99.3%), 100.0% (86.3%-100.0%), 93.3% (68.1%-99.8%), and 82.4% (56.6%-96.2%) at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In approximately half the study population, the M-protein concentration and involved FLC-ratio levels showed a yearly increase prior to MM diagnosis. In the present study, an asymptomatic MGUS stage consistently preceded MM. Novel molecular markers are needed to better predict progression to MM in patients with MGUS.

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 Impact of optimal follow-up of monoclonal gammopathy of undetermined significance on early diagnosis and prevention of myeloma-related complications

Blood ◽  
2010 ◽  
Vol 116 (12) ◽  
pp. 2019-2025 ◽  
Author(s):  
Giada Bianchi ◽  
Robert A. Kyle ◽  
Colin L. Colby ◽  
Dirk R. Larson ◽  
Shaji Kumar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Laboratory Testing ◽  
Monoclonal Gammopathy ◽  
Incidental Finding ◽  
Optimal Frequency ◽  
Future Studies ◽  
Risk Of Progression ◽  
Undetermined Significance

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is associated with a long-term risk of progression to multiple myeloma (MM) or related malignancy. To prevent serious myeloma-related complications, lifelong annual follow-up has been recommended, but its value is unknown. We reviewed all patients from southeastern Minnesota seen at Mayo Clinic between 1973 and 2004 with MGUS who subsequently progressed to MM. Of 116 patients, 69% had optimal follow-up of MGUS. Among these, abnormalities on serial follow-up laboratory testing led to the diagnosis of MM in 16%, whereas MM was diagnosed only after serious MM-related complications in 45%. In the remaining, workup of less serious symptoms (25%), incidental finding during workup of unrelated medical conditions (11%), and unknown (3%) were the mechanisms leading to MM diagnosis. High-risk MGUS patients (≥ 1.5 g/dL and/or non-IgG MGUS) were more likely to be optimally followed (81% vs 64%), and be diagnosed with MM secondary to serial follow-up testing (21% vs 7%). This retrospective study suggests that routine annual follow-up of MGUS may not be required in low-risk MGUS. Future studies are needed to replicate and expand our findings and to determine the optimal frequency of monitoring in higher-risk MGUS patients.

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

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.

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