Kristinsson SY, Pfeiffer RM, Björkholm M, et al. Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study. Blood. 2010;115(24):4991–4998.

Key PointsObesity is not associated with MGUS or LC-MGUS. High body mass index during midlife is associated with increased risk of progressing from MGUS and LC-MGUS to MM and other LP diseases.

Download Full-text

Parental longevity and survival among patients with multiple myeloma and monoclonal gammopathy of undetermined significance: a population‐based study

British Journal of Haematology ◽

10.1111/bjh.15883 ◽

2019 ◽

Vol 186 (1) ◽

pp. 37-44

Author(s):

Ingigerður S. Sverrisdóttir ◽

Sigrún H. Lund ◽

Ingemar Turesson ◽

Magnus Björkholm ◽

Lynn R. Goldin ◽

...

Keyword(s):

Multiple Myeloma ◽

Monoclonal Gammopathy ◽

Population Based ◽

Population Based Study ◽

Parental Longevity ◽

Undetermined Significance

Download Full-text

Familial Aggregation of Multiple Myeloma and Its Precursor Monoclonal Gammopathy of Undetermined Significance (MGUS): A Population-Based Study in Sweden.

Blood ◽

10.1182/blood.v112.11.1678.1678 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1678-1678

Author(s):

Sigurdur Y Kristinsson ◽

Magnus Bjorkholm ◽

Lynn R. Goldin ◽

Cecilie Blimark ◽

Ulf-Henrik Mellqvist ◽

...

Keyword(s):

Multiple Myeloma ◽

Hodgkin Lymphoma ◽

Monoclonal Gammopathy ◽

Familial Aggregation ◽

Large Population ◽

Population Based ◽

Case Control ◽

Population Based Study ◽

First Degree Relatives ◽

Undetermined Significance

Abstract Background: Evidence from multiply affected families, case-control and population-based registry studies implicate a role for genetic factors in multiple myeloma (MM). The aim of this large population-based familial case-control study was to quantify risks of MM, monoclonal gammopathy of undetermined significance (MGUS), and other lymphoproliferative disorders among first-degree relatives of MM patients. Methods: We identified 13,963 MM patients diagnosed in Swedish hospitals 1958–2005, with linkable relatives. Using the population-based central Population- and Multigenerational registries, we obtained 54,610 matched controls and first-degree relatives of MM patients (n=37,838) and controls (n=151,068). Relatives of MM patients and controls were linked with hospital-based outpatient registries and the central Swedish Cancer Registry to define occurrence of MGUS and lymphoproliferative malignancies. Measures of familial aggregation were calculated by a marginal survival model using relatives as the cohort. Results: First-degree relatives of MM patients had a significantly increased risk of developing MM [relative risk (RR)=2.1; (95% confidence interval (CI), 1.6–2.9)] and MGUS [2.1 (1.5–3.1)]. The risk estimates were very similar when we conducted analyses by gender of proband, by type of first-degree relative (parent, sibling, offspring), and by age at MM diagnosis (below/above 65 yrs) for probands. Among relatives of MM patients, we found no excess risk of chronic lymphocytic leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma, or lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia. Conclusions: In this large population-based study, we found relatives of MM patients to have a 2-fold excess risk of developing MM and MGUS compared with relatives of controls. Our findings support the theory that there are common, shared susceptibility genes that predispose to MM and MGUS. Better characterization of early genetic lesions mediating monoclonal plasma-cell proliferation, survival, and migration in the bone marrow microenvironment will potentially provide clues to pathogenesis and allow identification of novel molecular targets.

Download Full-text

Arterial and Venous Thrombosis in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma: A Population-Based Study.

Blood ◽

10.1182/blood.v114.22.1872.1872 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1872-1872 ◽

Cited By ~ 1

Author(s):

Sigurdur Y Kristinsson ◽

Ruth Pfeiffer ◽

Magnus Bjorkholm ◽

Lynn R Goldin ◽

Sam Schulman ◽

...

Keyword(s):

Multiple Myeloma ◽

Venous Thrombosis ◽

Arterial Thrombosis ◽

Monoclonal Gammopathy ◽

Population Based ◽

Excess Risk ◽

Thrombosis Prophylaxis ◽

Hazard Ratios ◽

Increased Risk ◽

Undetermined Significance

Abstract Abstract 1872 Poster Board I-897 Background Patients with multiple myeloma (MM) have an increased risk of venous thrombosis. Additionally, MM has been associated with arterial thrombosis. Interestingly, excess risk of venous thromboembolism has been observed among patients with monoclonal gammopathy of undetermined significance (MGUS). Methods Using population-based data from Sweden, we assessed the risks of venous and arterial thrombosis in 18,627 MM and 5,326 MGUS patients, compared to 70,991 and 20,161 matched controls, respectively. Hazard ratios for thrombosis, at 1, 5, and 10 years follow-up were calculated using Cox proportional hazard models. Results> At 1, 5 and 10 years after MM diagnosis, there was an increased risk of venous thrombosis: hazard ratios (95% confidence intervals) were 7.5 (6.4–8.9), 4.6 (4.1–5.1), and 4.1 (3.8–4.5), respectively. The corresponding results for arterial thrombosis were 1.9 (1.8–2.1), 1.5 (1.4–1.6), and 1.5 (1.4–1.5). At 1, 5 and 10 years after MGUS diagnosis, hazard ratios were 3.6 (2.6–4.9), 2.2 (1.8–2.6), and 2.1 (1.8–2.5) for venous thrombosis. The corresponding risks for arterial thrombosis were 1.7 (1.5–1.9), 1.3 (1.2–1.4), and 1.3 (1.3–1.4). IgG/IgA (but not IgM) MGUS patients had increased risks for venous and arterial thrombosis with hazard ratios 4.5 (2.8–7.2) and 1.6 (1.3–1.9) 1 year and 2.2 (1.7–2.8) and 1.2 (1.1–1.4) 5 years after diagnosis. Risks for thrombosis did not vary by M-protein concentration (above/below 10.0 g/L) at diagnosis. MGUS patients with (versus without) thrombosis had no excess risk of MM progression. Conclusion In this large study including more than 5,000 MGUS patients and 18,000 MM patients, and their matched controls, we found that both MGUS and MM patients had an increased risk of venous as well as arterial thrombosis. Among MGUS patients, an excess risk of thrombosis was observed in patients with IgG/IgA MGUS, but not IgM. Future studies are needed to clarify underlying mechanisms of our findings. Such efforts will be of relevance for physicians managing MGUS and MM patients and have potential implications for the development of better thrombosis prophylaxis strategies. Disclosures: Mellqvist: Johnson and Johnson: Research Funding; Celgene: Speakers Bureau; Jansen-Cilag: Speakers Bureau.

Download Full-text

Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study

Blood ◽

10.1182/blood-2009-11-252072 ◽

2010 ◽

Vol 115 (24) ◽

pp. 4991-4998 ◽

Cited By ~ 118

Author(s):

Sigurdur Y. Kristinsson ◽

Ruth M. Pfeiffer ◽

Magnus Björkholm ◽

Lynn R. Goldin ◽

Sam Schulman ◽

...

Keyword(s):

Multiple Myeloma ◽

Venous Thrombosis ◽

Arterial Thrombosis ◽

Monoclonal Gammopathy ◽

Population Based ◽

Excess Risk ◽

Thrombosis Prophylaxis ◽

Hazard Ratios ◽

Increased Risk ◽

Undetermined Significance

Abstract Patients with multiple myeloma (MM) have an increased risk of venous thrombosis. Interestingly, excess risk of venous thromboembolism has been observed among patients with monoclonal gammopathy of undetermined significance (MGUS). Using population-based data from Sweden, we assessed the risks of venous and arterial thrombosis in 18 627 MM and 5326 MGUS patients diagnosed from 1958 to 2006, compared with 70 991 and 20 161 matched controls, respectively. At 1, 5, and 10 years after MM diagnosis, there was an increased risk of venous thrombosis: hazard ratios (95% confidence intervals) were 7.5 (6.4-8.9), 4.6 (4.1-5.1), and 4.1 (3.8-4.5), respectively. The corresponding results for arterial thrombosis were 1.9 (1.8-2.1), 1.5 (1.4-1.6), and 1.5 (1.4-1.5). At 1, 5, and 10 years after MGUS diagnosis, hazard ratios were 3.4 (2.5-4.6), 2.1 (1.7-2.5), and 2.1 (1.8-2.4) for venous thrombosis. The corresponding risks for arterial thrombosis were 1.7 (1.5-1.9), 1.3 (1.2-1.4), and 1.3 (1.3-1.4). IgG/IgA (but not IgM) MGUS patients had increased risks for venous and arterial thrombosis. Risks for thrombosis did not vary by M-protein concentration (> 10.0 g/L or < 10.0 g/L) at diagnosis. MGUS patients with (vs without) thrombosis had no excess risk of MM or Waldenström macroglobulinemia. Our findings are of relevance for future studies and for improvement of thrombosis prophylaxis strategies.

Download Full-text

History of autoimmune disease is associated with impaired survival in multiple myeloma and monoclonal gammopathy of undetermined significance: a population-based study

Annals of Hematology ◽

10.1007/s00277-016-2859-8 ◽

2016 ◽

Vol 96 (2) ◽

pp. 261-269 ◽

Cited By ~ 8

Author(s):

Ebba K. Lindqvist ◽

Ola Landgren ◽

Sigrún H. Lund ◽

Ingemar Turesson ◽

Malin Hultcrantz ◽

...

Keyword(s):

Multiple Myeloma ◽

Autoimmune Disease ◽

Monoclonal Gammopathy ◽

Population Based ◽

Population Based Study ◽

History Of ◽

Undetermined Significance

Download Full-text

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

Blood Cancer Journal ◽

10.1038/s41408-021-00480-w ◽

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.

Download Full-text

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

Blood ◽

10.1182/blood-2008-12-194241 ◽

2009 ◽

Vol 113 (22) ◽

pp. 5412-5417 ◽

Cited By ~ 579

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.

Download Full-text

Peripheral neuropathy and monoclonal gammopathy of undetermined significance: A population-based study including 15,351 cases and 58,619 matched controls

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/j.clml.2019.09.541 ◽

2019 ◽

Vol 19 (10) ◽

pp. e329

Author(s):

Sæmundur Rögnvaldsson ◽

Vilhjálmur Steingrímsson ◽

Ingemar Turesson ◽

Magnus Björkholm ◽

C. Ola Landgren ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Monoclonal Gammopathy ◽

Population Based ◽

Population Based Study ◽

Undetermined Significance

Download Full-text

Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance

Blood ◽

10.1182/blood-2008-12-192575 ◽

2009 ◽

Vol 114 (4) ◽

pp. 785-790 ◽

Cited By ~ 85

Author(s):

Celine M. Vachon ◽

Robert A. Kyle ◽

Terry M. Therneau ◽

Barbara J. Foreman ◽

Dirk R. Larson ◽

...

Keyword(s):

Multiple Myeloma ◽

Monoclonal Gammopathy ◽

Population Based ◽

Detection Methods ◽

Shared Environment ◽

Serum Samples ◽

Adjusted Risk ◽

First Degree Relatives ◽

Increased Risk ◽

Undetermined Significance

Abstract We examined whether monoclonal gammopathy of undetermined significance (MGUS) is increased in first-degree relatives of multiple myeloma (MM) or MGUS patients. Probands were recruited from a population-based prevalence study (MGUS) and the Mayo Clinic (MM). Serum samples were collected from first-degree relatives older than 40 years and subjected to electrophoresis and immunofixation. The prevalence of MGUS in relatives was compared with population-based rates. Nine-hundred eleven relatives of 232 MM and 97 MGUS probands were studied. By electrophoresis, MGUS was detected in 55 (6%) relatives, and immunofixation identified 28 additional relatives for an age- and sex-adjusted prevalence of 8.1% (95% CI, 6.3 to 9.8). The prevalence of MGUS in relatives increased with age (1.9%, 6.9%, 11.6%, 14.6%, 21.0% for ages 40-49, 50-59, 60-69, 70-79, ≥ 80 years, respectively; P < .001). Using similar MGUS detection methods, there was a higher risk of MGUS in relatives (age-adjusted risk ratio [RR], 2.6; 95% CI, 1.9 to 3.4) compared with the reference population. The increased risk was seen among relatives of MM (RR, 2.0; 95% CI, 1.4 to 2.8) and MGUS probands (RR, 3.3; 95% CI, 2.1 to 4.8). The increased risk of MGUS in first-degree relatives of MGUS or MM patients implies shared environment and/or genetics.

Download Full-text