Materiały źródłowe

• #1 Monoclonal gammopathy of undetermined significance (MGUS) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/mgus/symptoms-causes/syc-20352362

  Monoclonal gammopathy of undetermined significance (MGUS) is a condition in which an atypical protein is found in the blood. […] People who have high amounts of this protein in the blood need regular checkups. That’s so they can get earlier treatment if the condition gets worse. If it doesn’t get worse, MGUS doesn’t need treatment. […] The average age at diagnosis is 70 years. […] Each year, about 1% of people with MGUS get certain types of blood cancers or other serious diseases, such as: Multiple myeloma. […] Diagnosis of monoclonal gammopathy of undetermined significance.

• #2 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507880/

  Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic preneoplastic plasma cell disorder that is characterized by serum M-protein less than 30 g/L, bone marrow clonal plasma cells less than 10 percent, absence of plasma cell myeloma-related end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions) and absence of B-cell lymphoma or other diseases known to produce an M-protein. […] Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell disorder that is characterized by the presence of serum M-protein less than 30 g/L or 3 g/dL, bone marrow (BM) clonal plasma cells less than 10%, absence of plasma cell myeloma (PCM) related end-organ damage (CRAB symptoms: hypercalcemia, renal insufficiency, anemia and, bone lesions) and absence of B-cell lymphoma or other disease known to produce an M-protein.

• #3 Diagnosis of monoclonal gammopathy of undetermined significance – UpToDate

  https://www.uptodate.com/contents/diagnosis-of-monoclonal-gammopathy-of-undetermined-significance

  Diagnosis of monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic premalignant clonal plasma cell or lymphoplasmacytic proliferative disorder. It is defined by the presence of a serum monoclonal protein (M protein) at a concentration <3 g/dL, a bone marrow with <10 percent monoclonal plasma cells, and absence of end-organ damage (lytic bone lesions, anemia, hypercalcemia, kidney impairment, hyperviscosity) related to the proliferative process. [...] MGUS occurs in over 3 percent of the White population over the age of 50 and is typically detected as an incidental finding when individuals undergo a protein electrophoresis as part of an evaluation for a wide variety of clinical symptoms and disorders (eg, peripheral neuropathy, vasculitis, hemolytic anemia, skin rashes, hypercalcemia, or elevated erythrocyte sedimentation rate).

• #4 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507880/

  Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic preneoplastic plasma cell disorder that is characterized by serum M-protein less than 30 g/L, bone marrow clonal plasma cells less than 10 percent, absence of plasma cell myeloma-related end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions) and absence of B-cell lymphoma or other diseases known to produce an M-protein. […] Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell disorder that is characterized by the presence of serum M-protein less than 30 g/L or 3 g/dL, bone marrow (BM) clonal plasma cells less than 10%, absence of plasma cell myeloma (PCM) related end-organ damage (CRAB symptoms: hypercalcemia, renal insufficiency, anemia and, bone lesions) and absence of B-cell lymphoma or other disease known to produce an M-protein.

• #5 How to Diagnose Monoclonal Gammopathy of Undetermined Significance

  https://consultqd.clevelandclinic.org/how-to-diagnose-monoclonal-gammopathy-of-undetermined-significance

  The monoclonal gammopathies encompass a number of disorders characterized by the production of a monoclonal protein (M protein) by an abnormal clone of plasma cells or other lymphoid cells. Monoclonal gammopathy of undetermined significance (MGUS) is the most common of these disorders. Its clinical relevance lies in the inherent risk of progression to hematologic malignancies such as multiple myeloma or other lymphoproliferative disorders, or of organ dysfunction due to the toxic effects of the M protein. […] Based on the International Myeloma Working Group consensus, a formal diagnosis of MGUS is established when a serum M protein is detected and measured at a concentration less than 3 g/dL on serum protein electrophoresis along with less than 10 percent clonal plasma cells in the bone marrow. Nevertheless, bone marrow biopsy can be omitted in certain patients as discussed below. The absence of myeloma-related organ damage particularly osteolytic bone lesions, anemia, otherwise unexplained renal failure and hypercalcemia is fundamental and necessary for a diagnosis of MGUS. […] Notably, weight loss and fatigue in a patient with MGUS may be the first signs of light-chain amyloidosis or Waldenstrm macroglobulinemia and should prompt further evaluation.

• #6 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507880/

  The majority of non-IgM MGUS patients are asymptomatic. According to the 2014 International Myeloma Working Group updated criteria, the diagnosis of non-IgM MGUS is based on three criteria: Serum monoclonal protein less than 30 g/L (3 g/dL), Less than 10% of clonal plasma cells in the bone marrow, The absence of CRAB symptoms (hypercalcemia, renal insufficiency, anemia and, bone lesions suspicious for PCM). […] Non-IgM MGUS is usually diagnosed as an incidental finding on protein electrophoresis performed as part of an evaluation for disorders or disease presentation of peripheral neuropathy, vasculitis, hemolytic anemia, skin rashes, hypercalcemia, elevated erythrocyte sedimentation rate. […] Non-IgM MGUS needs a thorough set of investigations to exclude this disease entity from the other plasma cell neoplasms.

• #7 What is the significance of monoclonal gammopathy of undetermined significance?

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6334115/

  Monoclonal gammopathy of undetermined significance (MGUS) is characterised by the presence of a monoclonal paraprotein in the blood, without the characteristic end organ damage seen in multiple myeloma. […] MGUS has three key diagnostic features: (a) the presence of a monoclonal paraprotein within the serum, at a level 30 g/L; (b) a proliferation of clonal plasma cells within the bone marrow, but forming 10% of the bone marrow; and (c) absence of features of the typical end-organ damage associated with multiple myeloma. […] Population-based screening for MGUS has not been recommended, as advised by the European Myeloma Network and by a joint recommendation from the UK Myeloma Forum and Nordic Myeloma Study Group. […] Currently, there is evidence that MGUS monitoring could lead to improvements in myeloma outcomes, although this evidence is limited.

• #8 Monoclonal gammopathy of undetermined significance – Wikipedia

  https://en.wikipedia.org/wiki/Monoclonal_gammopathy_of_undetermined_significance

  Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia in which plasma cells or other types of antibody-producing cells secrete a myeloma protein, i.e. an abnormal antibody, into the blood; this abnormal protein is usually found during standard laboratory blood or urine tests. MGUS resembles multiple myeloma and similar diseases, but the levels of antibodies are lower, the number of plasma cells (white blood cells that secrete antibodies) in the bone marrow is lower, and it rarely has symptoms or major problems. However, since MGUS can progress to multiple myeloma, with a rate ranging from 0.5% to 1.5% per year depending on the risk category, yearly monitoring is recommended. […] MGUS is a common, age-related medical condition characterized by an accumulation of bone marrow plasma cells derived from a single abnormal clone. Patients may be diagnosed with MGUS if they fulfill the following four criteria: A monoclonal paraprotein band less than 30 g/L ( 3g/dL); Plasma cells less than 10% on bone marrow examination; No evidence of bone lesions, anemia, hypercalcemia, or chronic kidney disease related to the paraprotein, and No evidence of another B-cell proliferative disorder.

• #9 Diagnosis of monoclonal gammopathy of undetermined significance – UpToDate

  https://www.uptodate.com/contents/diagnosis-of-monoclonal-gammopathy-of-undetermined-significance

  There are three distinct clinical types of MGUS, each with a risk of progressing through a unique intermediate (more advanced) premalignant stage and then to a malignant plasma cell dyscrasia or lymphoproliferative disorder: Non-IgM MGUS (IgG, IgA, or IgD MGUS) – Non-IgM MGUS is the most common subtype of MGUS and has the potential to progress to smoldering (asymptomatic) multiple myeloma and to symptomatic multiple myeloma. […] IgM MGUS – IgM MGUS accounts for approximately 15 percent of MGUS cases. It is considered separately from the non-IgM MGUS because it has the potential to progress to smoldering Waldenströ m macroglobulinemia and to symptomatic Waldenströ m macroglobulinemia, and less often to lymphoma or AL amyloidosis. Infrequently, IgM MGUS can progress to IgM multiple myeloma.

• #10 Diagnosis of monoclonal gammopathy of undetermined significance – UpToDate

  https://www.uptodate.com/contents/diagnosis-of-monoclonal-gammopathy-of-undetermined-significance

  There are three distinct clinical types of MGUS, each with a risk of progressing through a unique intermediate (more advanced) premalignant stage and then to a malignant plasma cell dyscrasia or lymphoproliferative disorder: Non-IgM MGUS (IgG, IgA, or IgD MGUS) – Non-IgM MGUS is the most common subtype of MGUS and has the potential to progress to smoldering (asymptomatic) multiple myeloma and to symptomatic multiple myeloma. […] IgM MGUS – IgM MGUS accounts for approximately 15 percent of MGUS cases. It is considered separately from the non-IgM MGUS because it has the potential to progress to smoldering Waldenströ m macroglobulinemia and to symptomatic Waldenströ m macroglobulinemia, and less often to lymphoma or AL amyloidosis. Infrequently, IgM MGUS can progress to IgM multiple myeloma.

• #11

  https://haematologica.org/article/view/7062

  Presenting features as well as the dynamics of the plasma cell clone during the first years of follow up are helpful in predicting risk of progression of MGUS to symptomatic disease. […] Biological characteristics of the clone also have predictive value in conventional MGUS and these include heavy chain isotype (IgA/IgM IgG); […] Detection of focal lesions by MRI at baseline […] or development of focal lesions by MRI or PET-CT predicted for progression to active MM. […] The importance of MGUS not only lies in the increased risk of developing a hematologic malignancy, but the small clone may also be responsible for severe organ damage through the production of a toxic M-protein which has autoantibody activity or deposits in tissues. […] MGUS patients have an approximately 2-fold increased risk of developing bacterial and viral infections compared to controls.

• #12 Monoclonal Gammopathy of Undetermined Significance (MGUS)

  https://my.clevelandclinic.org/health/diseases/17744-monoclonal-gammopathy-of-undetermined-significance-mgus

  Monoclonal gammopathy of undetermined significance (MGUS) is a blood disorder that affects plasma cells in your bone marrow. Most of the time, M proteins dont cause issues and most people with MGUS dont have symptoms. Healthcare providers often discover this condition after taking blood or urine samples as part of a routine physical examination. Providers typically do blood and urine tests every six to 12 months to look for signs that monoclonal gammopathy of undetermined significance is becoming a more serious medical problem. […] Providers analyze your blood and urine for signs of M protein. They also evaluate other factors to establish the risk MGUS will become cancer or a more serious blood disorder. These risk factors include: The amount of M protein in your blood. The type of M protein in your blood. The amount of free light chains in your blood. Free light chains (FLC) are proteins made by plasma cells. FLC tests detect abnormal concentrations of free light chains. […] Most people with this condition dont need treatment. While MGUS rarely becomes cancerous, your provider will monitor M protein levels in your blood and urine (pee) every six to 12 months for signs of cancer.

• #13 Monoclonal gammopathy of undetermined significance (MGUS) – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/mgus/diagnosis-treatment/drc-20352367

  Because MGUS usually causes no symptoms, people who have it usually find out by chance during blood tests for other reasons. […] After that, other tests might include: […] More blood tests. These can help rule out other causes of higher protein levels. And they can check for kidney damage. […] Urine tests. Urine samples taken over 24 hours can help find if the atypical protein is in the urine. They also can check for kidney damage. […] Imaging tests. For people with bone pain, an MRI or positron emission tomography (PET) scan can look for problems with bones from MGUS. They also might need a test to measure bone mass, also known as bone density. […] Bone marrow test. A hollow needle removes a piece of bone marrow from the back of one of the hipbones for study. This usually is only for those at risk of getting a more serious disease or other problems linked to MGUS.

• #14 Monoclonal gammopathy of undetermined significance (MGUS) – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/mgus/diagnosis-treatment/drc-20352367

  Because MGUS usually causes no symptoms, people who have it usually find out by chance during blood tests for other reasons. […] After that, other tests might include: […] More blood tests. These can help rule out other causes of higher protein levels. And they can check for kidney damage. […] Urine tests. Urine samples taken over 24 hours can help find if the atypical protein is in the urine. They also can check for kidney damage. […] Imaging tests. For people with bone pain, an MRI or positron emission tomography (PET) scan can look for problems with bones from MGUS. They also might need a test to measure bone mass, also known as bone density. […] Bone marrow test. A hollow needle removes a piece of bone marrow from the back of one of the hipbones for study. This usually is only for those at risk of getting a more serious disease or other problems linked to MGUS.

• #15 What Is MGUS? – Monoclonal Gammopathy of Undetermined Significance | Roswell Park Comprehensive Cancer Center – Buffalo, NY

  https://www.roswellpark.org/cancer/multiple-myeloma/about/mgus

  MGUS is caused by monoclonal plasma cells. Monoclonal means we think they all began from the same cell. […] The antibodies produced by those abnormal cells are called monoclonal proteins (M-proteins), and they can be measured in the blood and urine. […] The following tests may be required to diagnose MGUS and determine that it is not a symptom-causing disease: […] Bone marrow biopsy, to find out how many monoclonal plasma cells are in your bone marrow (This is performed only in patients with certain characteristics of MGUS.) […] A urine sample (collected over a 24-hour period) and blood draw, to find out how much M-protein is in your urine and serum. […] A blood draw, to find out how much calcium is in your blood and whether your kidneys are functioning normally. […] Magnetic Resonance Imaging (MRI) or Positron Emission Tomography and Computed Tomography (PET-CT), to find out whether there are holes in your bones (This is performed only in patients with certain characteristics of MGUS.)

• #16 Monoclonal Gammopathy of Unknown Significance (MGUS) | UAMS Health

  https://uamshealth.com/condition/monoclonal-gammopathy-of-unknown-significance/

  Monoclonal Gammopathy of Undetermined Significance (MGUS) is a non-cancerous, or benign, condition characterized by the presence in the blood of an abnormal protein produced by plasma cells. […] MGUS is clinically defined as having a paraprotein level of less than 3 grams per deciliter and less than 10 percent plasma cells in the bone marrow. There is no damage to bones, calcium levels are normal, little or no protein is present in the urine, kidney function is normal and there is no anemia (which can result from a low red blood cell count). […] The diagnosis is then confirmed by having a particular blood test called serum electropheresis which identifies the abnormal antibody.

• #17

  https://link.springer.com/article/10.1007/s12254-020-00630-z

  Several risk factors for progression have been identified. An Mspike of 15g/L is the most important determinant for progression. […] Based on the known risk factors, Rajkumar et al. developed a model that incorporates the following biomarkers: non-IgG MGUS, Mprotein of 15g/L, and abnormal free light chain (FLC) ratio of 0.125 or 8. […] Due to its high prevalence in the elderly population, screening for MGUS is not recommended, even though it has been suggested that MM is virtually always preceded by MGUS and early detection and subsequent close monitoring may prevent the occurrence of end-organ damage. […] Once detected, any paraprotein always warrants thorough work-up. […] Laboratory testing should include a complete blood count with differential, blood chemistry, serum and urine electrophoresis with immunofixation, and measurement of FLCs. […] In all other patients, i.e. IgA or IgM subtypes, an M-protein of 15g/L, or an abnormal FLC ratio, bone marrow biopsy is recommended. […] Follow-up should be lifelong and risk-based, focusing on the early detection of end-organ damage.

• #18 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507880/

  The majority of non-IgM MGUS patients are asymptomatic. According to the 2014 International Myeloma Working Group updated criteria, the diagnosis of non-IgM MGUS is based on three criteria: Serum monoclonal protein less than 30 g/L (3 g/dL), Less than 10% of clonal plasma cells in the bone marrow, The absence of CRAB symptoms (hypercalcemia, renal insufficiency, anemia and, bone lesions suspicious for PCM). […] Non-IgM MGUS is usually diagnosed as an incidental finding on protein electrophoresis performed as part of an evaluation for disorders or disease presentation of peripheral neuropathy, vasculitis, hemolytic anemia, skin rashes, hypercalcemia, elevated erythrocyte sedimentation rate. […] Non-IgM MGUS needs a thorough set of investigations to exclude this disease entity from the other plasma cell neoplasms.

• #19

  https://www.ashclinicalnews.org/training-education/treat-brief-managing-monoclonal-gammopathy-undetermined-significance/

  Although MGUS, by definition, requires BM clonal plasma cells to be less than 10 percent and no evidence of lytic lesions on skeletal imaging, not all patients with suspected MGUS need these tests. […] For all other patients with MGUS, we perform BM biopsy and skeletal imaging at the time of diagnosis. […] The purpose of follow-up is to detect early progression of MGUS into LPM, with the expectation that timely treatment will minimize major complications and prolong survival. […] Despite a lack of prospective data from randomized trials, clinical practice guidelines recommend annual follow-up for most patients with MGUS, given the seriousness of LPM complications and the relative ease of testing for M-proteins. […] A rising M-protein or serum FLC level should raise concern about disease progression, but these elevations are seen in only about 50 percent of patients with MGUS prior to progression.

• #20 Monoclonal Gammopathies of Undetermined Significance (MGUS) Differential Diagnoses

  https://emedicine.medscape.com/article/204297-differential

  Monoclonal gammopathy of undetermined significance (MGUS) must be differentiated from myoclonal gammopathy of renal significance (MGRS), multiple myeloma (MM), and smoldering MM (SMM). Criteria for MGUS established by the International Myeloma Working Group and the World Health Organization are as follows: […] In clinical and biologic terms, SMM is closer to MGUS than to overt MM. Recognition of patients with SMM is extremely important because they should not be treated with chemotherapy until progression occurs. […] Although Bence-Jones proteinuria suggests MM, finding small amounts of monoclonal light chains in the urine of patients with MGUS is not unusual. […] In patients recently diagnosed with MGUS, serum electrophoresis should be repeated after 3 months to exclude early myeloma, and, if the results are stable, the test should be repeated in 6 months. Patients should be aware that the evolution of MGUS to MM can be abrupt; therefore, they should be reexamined promptly if their clinical condition deteriorates.

• #21 Benign monoclonal gammopathy (monoclonal gammopathy of unknown significance) – Cancer Therapy Advisor

  https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/hospital-medicine/benign-monoclonal-gammopathy-monoclonal-gammopathy-of-unknown-significance/

  Benign monoclonal gammopathy is an abnormal clonal disorder of plasma cells. Also known as monoclonal gammopathy of unknown significance (MGUS), benign monoclonal gammopathy is, by definition, an asymptomatic condition. […] However, benign monoclonal gammopathy (from here forward referred to as MGUS) is also a pre-malignant condition in that patients with this condition will progress to multiple myeloma or another malignancy at a rate of approximately 1% per year. […] The approach to MGUS is focused on two key points: ruling out another syndrome associated with a monoclonal gammopathy and assessing the risk of progression to a malignant disorder. […] To make the diagnosis, the clinician must establish two key findings: A monoclonal gammopathy seen on serum protein electrophoresis (or serum immunofixation) and absence of symptoms related to the monoclonal gammopathy.

• #22 Monoclonal Gammopathies of Undetermined Significance (MGUS) Differential Diagnoses

  https://emedicine.medscape.com/article/204297-differential

  Monoclonal gammopathy of undetermined significance (MGUS) must be differentiated from myoclonal gammopathy of renal significance (MGRS), multiple myeloma (MM), and smoldering MM (SMM). Criteria for MGUS established by the International Myeloma Working Group and the World Health Organization are as follows: […] In clinical and biologic terms, SMM is closer to MGUS than to overt MM. Recognition of patients with SMM is extremely important because they should not be treated with chemotherapy until progression occurs. […] Although Bence-Jones proteinuria suggests MM, finding small amounts of monoclonal light chains in the urine of patients with MGUS is not unusual. […] In patients recently diagnosed with MGUS, serum electrophoresis should be repeated after 3 months to exclude early myeloma, and, if the results are stable, the test should be repeated in 6 months. Patients should be aware that the evolution of MGUS to MM can be abrupt; therefore, they should be reexamined promptly if their clinical condition deteriorates.

• #23 Monoclonal Gammopathy of Undetermined Significance – MD Searchlight

  https://mdsearchlight.com/blood-disorders/monoclonal-gammopathy-of-undetermined-significance/

  Identifying non-IgM MGUS from other severe plasma cell diseases is crucial as it can lead to different treatment plans. There are other conditions that may appear similar to non-IgM MGUS, which include: Plasma cell myeloma (smoldering or symptomatic), Waldenstrm macroglobulinemia (smoldering or symptomatic), Monoclonal gammopathy of renal significance, Light chain smoldering multiple myeloma (idiopathic Bence Jones proteinuria), Primary (amyloid light chain) amyloidosis and light chain deposition disease, B cell lymphoproliferative disorder. […] Non-IgM MGUS is understood to be a condition that could potentially lead to cancer, with roughly a 1% risk of progression each year. The risk can increase when there is a higher than normal level of M protein or an abnormal free light chain ratio, which is a type of blood test. Treatment isnt usually required for Non-IgM MGUS. However, managing this condition relies on knowing the chance of the disease advancing. Regular check-ups are generally recommended.

• #24

  https://haematologica.org/article/view/7062

  The risk of progression for light-chain MGUS is lower when compared to conventional MGUS. […] MGUS patients have a poorer survival than the general population. […] MGUS patients have an increased risk of osteoporosis and fractures (axial distal). […] The M-protein seems to play a role in the development of several skin disorders including plane xanthoma and Schnitzler syndrome. […] The M-protein may act as an anti-platelet autoantibody. […] The M-protein is the direct cause of the kidney disease and these disorders are characterized by the presence of monoclonal deposits in the kidney. […] Importantly, M-protein-associated kidney diseases have a high recurrence rate after kidney transplantation. […] Treatment of M-protein-related disorders is dependent on severity. […] These recommendations are personalized and based on both life expectancy and risk of progression.

• #25 Monoclonal Gammopathy of Undetermined Significance (MGUS)

  https://my.clevelandclinic.org/health/diseases/17744-monoclonal-gammopathy-of-undetermined-significance-mgus

  Monoclonal gammopathy of undetermined significance (MGUS) is a blood disorder that affects plasma cells in your bone marrow. Most of the time, M proteins dont cause issues and most people with MGUS dont have symptoms. Healthcare providers often discover this condition after taking blood or urine samples as part of a routine physical examination. Providers typically do blood and urine tests every six to 12 months to look for signs that monoclonal gammopathy of undetermined significance is becoming a more serious medical problem. […] Providers analyze your blood and urine for signs of M protein. They also evaluate other factors to establish the risk MGUS will become cancer or a more serious blood disorder. These risk factors include: The amount of M protein in your blood. The type of M protein in your blood. The amount of free light chains in your blood. Free light chains (FLC) are proteins made by plasma cells. FLC tests detect abnormal concentrations of free light chains. […] Most people with this condition dont need treatment. While MGUS rarely becomes cancerous, your provider will monitor M protein levels in your blood and urine (pee) every six to 12 months for signs of cancer.

• #26 Monoclonal gammopathy of undetermined significance: A primary care guide | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/86/1/39

  Monoclonal gammopathy of undetermined significance (MGUS) is commonly diagnosed in outpatients being worked up for an array of clinical concerns. It carries a risk of progression to myeloma and other lymphoproliferative disorders that, albeit low (1% per year), warrants regular follow-up. Patients with MGUS can be risk-stratified on the basis of the amount and type of their monoclonal protein as well as whether they have an abnormal light-chain ratio. Here, we provide a guide to the diagnosis, workup, and management of MGUS. […] The overall risk of MGUS progressing to myeloma and other lymphoproliferative disorders is 1% per year. […] Low-risk MGUS is defined by an immunoglobulin G monoclonal protein at a concentration less than 1.5 g/dL and a normal serum free light-chain ratio. […] Based on the International Myeloma Working Group consensus, a formal diagnosis of MGUS is established when a serum M protein is detected and measured at a concentration less than 3 g/dL on serum protein electrophoresis along with less than 10% clonal plasma cells in the bone marrow.

• #27 Diagnosis and Follow-Up of MGUSlogo-32logo-40logo-60NEJM Journal WatchnejmJW_1L_RGB-b

  https://www.jwatch.org/na51573/2020/05/14/diagnosis-and-follow-mgus

  When MGUS is discovered, an international guideline suggests follow-up according to risk for malignant transformation (Leukemia 2010; 24:1121). […] For example, low-risk patients (i.e., serum M protein <1.5 g/dL, IgG subtype, and normal free light chain ratio) should be reevaluated at 6 months; if results are stable, repeat testing can be every 2 to 3 years or even not at all (unless the patient develops symptoms suggesting plasma cell malignancy). [...] Closer follow-up is suggested for higher-risk patients.

• #28

  https://link.springer.com/article/10.1007/s12254-020-00630-z

  Several risk factors for progression have been identified. An Mspike of 15g/L is the most important determinant for progression. […] Based on the known risk factors, Rajkumar et al. developed a model that incorporates the following biomarkers: non-IgG MGUS, Mprotein of 15g/L, and abnormal free light chain (FLC) ratio of 0.125 or 8. […] Due to its high prevalence in the elderly population, screening for MGUS is not recommended, even though it has been suggested that MM is virtually always preceded by MGUS and early detection and subsequent close monitoring may prevent the occurrence of end-organ damage. […] Once detected, any paraprotein always warrants thorough work-up. […] Laboratory testing should include a complete blood count with differential, blood chemistry, serum and urine electrophoresis with immunofixation, and measurement of FLCs. […] In all other patients, i.e. IgA or IgM subtypes, an M-protein of 15g/L, or an abnormal FLC ratio, bone marrow biopsy is recommended. […] Follow-up should be lifelong and risk-based, focusing on the early detection of end-organ damage.

• #29

  https://haematologica.org/article/view/7062

  Presenting features as well as the dynamics of the plasma cell clone during the first years of follow up are helpful in predicting risk of progression of MGUS to symptomatic disease. […] Biological characteristics of the clone also have predictive value in conventional MGUS and these include heavy chain isotype (IgA/IgM IgG); […] Detection of focal lesions by MRI at baseline […] or development of focal lesions by MRI or PET-CT predicted for progression to active MM. […] The importance of MGUS not only lies in the increased risk of developing a hematologic malignancy, but the small clone may also be responsible for severe organ damage through the production of a toxic M-protein which has autoantibody activity or deposits in tissues. […] MGUS patients have an approximately 2-fold increased risk of developing bacterial and viral infections compared to controls.

• #30 Monoclonal Gammopathies of Undetermined Significance (MGUS): Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/204297-overview

  The annual risk of progression to multiple myeloma (MM), Waldenstrm macroglobulinemia (WM), amyloidosis (AL), or other lymphoproliferative disorders is approximately 1%. However, the mode and risk of progression vary between IgM MGUS and those with non-IgM MGUS. […] An abnormal serum free light-chain ratio (ratio of kappa to lambda free light chains) and a high serum monoclonal protein (M protein) level (1.5 g per deciliter) are risk factors for progression. […] In a study of 728 Swedish MGUS patients followed for up to 30 years, 84 patients developed a lymphoid disorder, representing a cumulative risk of 15.4%. The 30-year cumulative risk for myeloid malignancies was less than 2%. The 30-year cumulative risk for MM, which occurred in 53 patients, was 10.6%, with an approximately 0.5% annual risk. […] Although autoimmune disease is a well-described risk factor for the development of MGUS, a Swedish population-based study determined that patients with a history of autoimmune disease have a significantly lower risk of progression from MGUS to MM or other lymphoproliferative diseases.

• #31 Management of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM)

  https://www.cancernetwork.com/view/management-monoclonal-gammopathy-undetermined-significance-mgus-and-smoldering-multiple-myeloma-smm

  The cause of MGUS is not known. […] MGUS is a common finding in medical practice. It is asymptomatic and is found unexpectedly during laboratory testing of an apparently normal person, or it may be found during the evaluation of an unrelated disorder. […] The size of the M protein at the time of recognition of MGUS is the most important predictor of progression. […] A risk stratification model for predicting the risk of progression of MGUS using simple laboratory markers has been developed. […] Clinical and laboratory findings are helpful in differentiating a patient with MGUS from one with MM. […] At follow-up, after MGUS has first been recognized, a complete history and physical examination should be performed with emphasis on symptoms and findings that might suggest AL amyloidosis or MM.

• #32 Monoclonal Gammopathy of Undetermined Significance (MGUS) ​

  https://watch.giblib.com/video/10267

  If you were to take MGUS, I just mentioned earlier that the risk of progression is roughly about 1% per year, but work here at the Mayo Clinic really showed that you can take all these patients. […] If you have none of those, you have zero points. You are in the low risk MGUS category. […] If you have one of those, then you’re in the low intermediate risk. If you have two of those factors, you’re in the high intermediate risk. And if you have all three of those factors, then you’re in the high risk. […] So once we have a patient who have been diagnosed with MGUS, do they need the same tests annually for follow up? […] And Dr. Gale has shown this even with his most recent follow up, as long as 40 years, that that that risk of progression is always there at roughly an average of 1% per year, even 30 years out or ten years out or 15 years. […] And right now, there’s nothing that has been time tested or proven to prevent the progression of MGUS to multiple myeloma.

• #33 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507880/

  Treatment is usually not recommended for patients with MGUS. As there is a risk of progression to lymphoproliferative malignancy long-term follow-up is advised. […] The intensity of follow-up in patients with MGUS is guided by risk stratification. Initial follow-up at six months is recommended, with subsequent visits scheduled according to the level of risk. […] Non-IgM MGUS is considered a preneoplastic condition with an annual risk of progression of approximately 1%. […] Monoclonal gammopathy of undetermined significance (MGUS) can progress to develop myeloproliferative disorders or other serious conditions such as multiple myeloma, light chain amyloidosis, Waldenstrom macroglobulinemia, lymphoma, osteoporosis, and venous thromboembolism. […] Monoclonal gammopathy of undetermined significance (MGUS) patients have no specific treatment, they should undergo detail clinical examination, serum, and urine protein electrophoresis regularly every six to twelve months to look for disease progression. […] Monoclonal gammopathy of undetermined significance (MGUS) is best managed by an interprofessional team that includes primary care providers, hematologists, medical oncologists, and nurses.

• #34 Monoclonal gammopathy of undetermined significance (MGUS) – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/mgus/diagnosis-treatment/drc-20352367

  MGUS doesn’t require treatment. But your health care provider is likely to have you get regular checkups to watch the condition. Checkups likely will start six months after your diagnosis. […] For those at high risk of MGUS leading to a more serious condition, more-frequent checkups can watch the disease. That way, treatment can start as soon as possible if it’s needed. […] For MGUS, basic questions to ask your provider include: […] What tests do I need? […] How often do I need to come back? […] Should I start treatment or change my lifestyle? […] Your health care provider is likely to ask you questions, including: […] Has someone in your family had MGUS?

• #35 Monoclonal gammopathy of undetermined significance | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/multiple-myeloma/what-is-multiple-myeloma/monoclonal-gammopathy-of-undetermined-significance

  Recently, diagnostic tests have helped to identify which people with MGUS have a low risk and which have a high risk of developing multiple myeloma and other conditions including amyloidosis, solitary plasmacytoma or Waldenstrom macroglobulinemia. […] When you are diagnosed with MGUS, you will be closely monitored (watched) by your healthcare team for signs of the disease progressing to multiple myeloma or a related condition. This is called watchful waiting. Other treatment is given when MGUS starts to progress to cancer. […] Follow-up visits are scheduled differently for low-risk MGUS and high-risk MGUS.

• #36 Diagnosis and Follow-Up of MGUSlogo-32logo-40logo-60NEJM Journal WatchnejmJW_1L_RGB-b

  https://www.jwatch.org/na51573/2020/05/14/diagnosis-and-follow-mgus

  When MGUS is discovered, an international guideline suggests follow-up according to risk for malignant transformation (Leukemia 2010; 24:1121). […] For example, low-risk patients (i.e., serum M protein <1.5 g/dL, IgG subtype, and normal free light chain ratio) should be reevaluated at 6 months; if results are stable, repeat testing can be every 2 to 3 years or even not at all (unless the patient develops symptoms suggesting plasma cell malignancy). [...] Closer follow-up is suggested for higher-risk patients.

• #37 Monoclonal Gammopathy of Undetermined Significance (MGUS) – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/plasma-cell-disorders/monoclonal-gammopathy-of-undetermined-significance-mgus

  Monoclonal gammopathy of undetermined significance (MGUS) is the production of M-protein by noncancerous plasma cells in the absence of other manifestations typical of multiple myeloma. […] The diagnosis of MGUS is usually suspected when the M-protein is incidentally detected in blood or urine during a routine examination or as part of the evaluation for an unexplained peripheral neuropathy. On laboratory evaluation, M-protein is present in lower levels in serum ( 3 g/dL [ 200 mg/24 hours) than among patients with multiple myeloma. MGUS is differentiated from malignant plasma cell disorders because M-protein levels are lower, clonal plasma cells in bone marrow are lower, and lytic bone lesions, anemia, and renal dysfunction are absent. […] Every 6 to 12 months, patients should undergo clinical examination and serum and urine protein electrophoresis to evaluate for disease progression.

• #38

  https://www.ashclinicalnews.org/training-education/treat-brief-managing-monoclonal-gammopathy-undetermined-significance/

  Although MGUS, by definition, requires BM clonal plasma cells to be less than 10 percent and no evidence of lytic lesions on skeletal imaging, not all patients with suspected MGUS need these tests. […] For all other patients with MGUS, we perform BM biopsy and skeletal imaging at the time of diagnosis. […] The purpose of follow-up is to detect early progression of MGUS into LPM, with the expectation that timely treatment will minimize major complications and prolong survival. […] Despite a lack of prospective data from randomized trials, clinical practice guidelines recommend annual follow-up for most patients with MGUS, given the seriousness of LPM complications and the relative ease of testing for M-proteins. […] A rising M-protein or serum FLC level should raise concern about disease progression, but these elevations are seen in only about 50 percent of patients with MGUS prior to progression.

• #39 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507880/

  Treatment is usually not recommended for patients with MGUS. As there is a risk of progression to lymphoproliferative malignancy long-term follow-up is advised. […] The intensity of follow-up in patients with MGUS is guided by risk stratification. Initial follow-up at six months is recommended, with subsequent visits scheduled according to the level of risk. […] Non-IgM MGUS is considered a preneoplastic condition with an annual risk of progression of approximately 1%. […] Monoclonal gammopathy of undetermined significance (MGUS) can progress to develop myeloproliferative disorders or other serious conditions such as multiple myeloma, light chain amyloidosis, Waldenstrom macroglobulinemia, lymphoma, osteoporosis, and venous thromboembolism. […] Monoclonal gammopathy of undetermined significance (MGUS) patients have no specific treatment, they should undergo detail clinical examination, serum, and urine protein electrophoresis regularly every six to twelve months to look for disease progression. […] Monoclonal gammopathy of undetermined significance (MGUS) is best managed by an interprofessional team that includes primary care providers, hematologists, medical oncologists, and nurses.

• #40 Management of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM)

  https://www.cancernetwork.com/view/management-monoclonal-gammopathy-undetermined-significance-mgus-and-smoldering-multiple-myeloma-smm

  The cause of MGUS is not known. […] MGUS is a common finding in medical practice. It is asymptomatic and is found unexpectedly during laboratory testing of an apparently normal person, or it may be found during the evaluation of an unrelated disorder. […] The size of the M protein at the time of recognition of MGUS is the most important predictor of progression. […] A risk stratification model for predicting the risk of progression of MGUS using simple laboratory markers has been developed. […] Clinical and laboratory findings are helpful in differentiating a patient with MGUS from one with MM. […] At follow-up, after MGUS has first been recognized, a complete history and physical examination should be performed with emphasis on symptoms and findings that might suggest AL amyloidosis or MM.

• #41 Precursor Conditions to Multiple Myeloma | Myeloma Center

  https://www.myelomacenter.org/patients/other-plasma-cell-disorders/precursor-conditions-multiple-myeloma

  MGUS often presents with no symptoms, but occasionally symptoms such as a rash or nerve problems like numbness or tingling may occur. Developing additional symptoms such as bone pain, fatigue, weakness, weight loss, fever, night sweats, headache, dizziness, nerve pain, bleeding, anemia, or swollen lymph nodes may indicate disease progression. […] Although MGUS is usually silent and does not cause overt symptoms, rarely, monoclonal proteins can damage vital organs. This is usually suspected in individuals who present with unexplained symptoms. The kidneys, peripheral nerves, and skin can be among the organs most often affected. When this is suspected, a further work up might be warranted including biopsies or referral to a specialist such as a dermatologist, neurologist, or nephrologist. Treatment is available in certain cases including IV immunoglobulin, rituximab, and plasma celldirected therapies.

• #42 Monoclonal Gammopathies of Undetermined Significance (MGUS) Differential Diagnoses

  https://emedicine.medscape.com/article/204297-differential

  Monoclonal gammopathy of undetermined significance (MGUS) must be differentiated from myoclonal gammopathy of renal significance (MGRS), multiple myeloma (MM), and smoldering MM (SMM). Criteria for MGUS established by the International Myeloma Working Group and the World Health Organization are as follows: […] In clinical and biologic terms, SMM is closer to MGUS than to overt MM. Recognition of patients with SMM is extremely important because they should not be treated with chemotherapy until progression occurs. […] Although Bence-Jones proteinuria suggests MM, finding small amounts of monoclonal light chains in the urine of patients with MGUS is not unusual. […] In patients recently diagnosed with MGUS, serum electrophoresis should be repeated after 3 months to exclude early myeloma, and, if the results are stable, the test should be repeated in 6 months. Patients should be aware that the evolution of MGUS to MM can be abrupt; therefore, they should be reexamined promptly if their clinical condition deteriorates.

• #43 Monoclonal gammopathy of undetermined significance (MGUS) – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/mgus/symptoms-causes/syc-20352362

  Monoclonal gammopathy of undetermined significance (MGUS) is a condition in which an atypical protein is found in the blood. […] People who have high amounts of this protein in the blood need regular checkups. That’s so they can get earlier treatment if the condition gets worse. If it doesn’t get worse, MGUS doesn’t need treatment. […] The average age at diagnosis is 70 years. […] Each year, about 1% of people with MGUS get certain types of blood cancers or other serious diseases, such as: Multiple myeloma. […] Diagnosis of monoclonal gammopathy of undetermined significance.

• #44 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507880/

  Treatment is usually not recommended for patients with MGUS. As there is a risk of progression to lymphoproliferative malignancy long-term follow-up is advised. […] The intensity of follow-up in patients with MGUS is guided by risk stratification. Initial follow-up at six months is recommended, with subsequent visits scheduled according to the level of risk. […] Non-IgM MGUS is considered a preneoplastic condition with an annual risk of progression of approximately 1%. […] Monoclonal gammopathy of undetermined significance (MGUS) can progress to develop myeloproliferative disorders or other serious conditions such as multiple myeloma, light chain amyloidosis, Waldenstrom macroglobulinemia, lymphoma, osteoporosis, and venous thromboembolism. […] Monoclonal gammopathy of undetermined significance (MGUS) patients have no specific treatment, they should undergo detail clinical examination, serum, and urine protein electrophoresis regularly every six to twelve months to look for disease progression. […] Monoclonal gammopathy of undetermined significance (MGUS) is best managed by an interprofessional team that includes primary care providers, hematologists, medical oncologists, and nurses.

• #45

  https://haematologica.org/article/view/7062

  Monoclonal gammopathy of undetermined significance is one of the most common pre-malignant disorders. […] Clonal burden, as determined by bone marrow plasma cell percentage or M-protein level, as well as biological characteristics, including heavy chain isotype and light chain production, are helpful in predicting risk of progression of monoclonal gammopathy of undetermined significance to symptomatic disease. […] In this review, we provide an overview of the clinical relevance of monoclonal gammopathy of undetermined significance. We also give general recommendations of how to diagnose and manage patients with monoclonal gammopathy of undetermined significance. […] There is an average risk of progression to MM or, to a lesser extent, other lymphoproliferative disorders of 1% per year.

• #46 Monoclonal Gammopathy of Undetermined Significance – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507880/

  Treatment is usually not recommended for patients with MGUS. As there is a risk of progression to lymphoproliferative malignancy long-term follow-up is advised. […] The intensity of follow-up in patients with MGUS is guided by risk stratification. Initial follow-up at six months is recommended, with subsequent visits scheduled according to the level of risk. […] Non-IgM MGUS is considered a preneoplastic condition with an annual risk of progression of approximately 1%. […] Monoclonal gammopathy of undetermined significance (MGUS) can progress to develop myeloproliferative disorders or other serious conditions such as multiple myeloma, light chain amyloidosis, Waldenstrom macroglobulinemia, lymphoma, osteoporosis, and venous thromboembolism. […] Monoclonal gammopathy of undetermined significance (MGUS) patients have no specific treatment, they should undergo detail clinical examination, serum, and urine protein electrophoresis regularly every six to twelve months to look for disease progression. […] Monoclonal gammopathy of undetermined significance (MGUS) is best managed by an interprofessional team that includes primary care providers, hematologists, medical oncologists, and nurses.

• #47 What is the significance of monoclonal gammopathy of undetermined significance?

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6334115/

  The accumulating evidence around MGUS, its impact on health and the ability to reduce or mitigate health impacts supports the proposal that MGUS fulfils many of the criteria needed to implement a screening programme. […] Monoclonal gammopathy of undetermined significance carries a risk of progression to myeloma and is associated with several complications, including renal impairment, infection and fracture, which can have not only significant morbidity but also potential treatments.

• #48 Monoclonal Gammopathy of Undetermined Significance (MGUS) | Memorial Sloan Kettering Cancer Center

  https://www.mskcc.org/cancer-care/types/multiple-myeloma/other-plasma-cell-diseases/monoclonal-gammopathy-undetermined-significance

  Monoclonal gammopathy of undetermined significance (MGUS) is not cancer. Theres a small risk it can become cancer. Out of every 100 people with MGUS, each year, 1 or 2 of them will get cancer from MGUS. […] Blood and urine tests can show if you have MGUS, or show signs its getting worse. These tests look for how much m-protein is in your blood, and what kind of m-protein you have. […] If you have MGUS, your protein levels should be monitored through regular blood tests. You will not need treatment for MGUS as long as the level of m-protein does not rise. […] They will watch to see if MGUS becomes another blood disease. If that happens, your MSK doctors can treat plasma cell disorders or multiple myeloma.

• #49 Monoclonal Gammopathy of Undetermined Significance (MGUS)—Not So Asymptomatic after All

  https://www.mdpi.com/2072-6694/12/6/1554

  Monoclonal Gammopathy of Undetermined Significance (MGUS) is considered to be a benign precursor condition that may progress to a lymphoproliferative disease or multiple myeloma. Most patients do not progress to an overt condition, but nevertheless, MGUS is associated with a shortened life expectancy and, in a minority of cases, a number of co-morbid conditions that include an increased fracture risk, renal impairment, peripheral neuropathy, secondary immunodeficiency, and cardiovascular disease. […] Monoclonal Gammopathy of Undetermined Significance (MGUS) is characterized by the presence of a serum monoclonal paraprotein derived from immunoglobulin (Ig). MGUS may be classified into IgM and non-IgM MGUS, depending on the cellular clone responsible for the particular paraprotein. […] Even though the vast majority of the cases of MM arise from a prior state of MGUS, overall, the annual risk of progression from MGUS to symptomatic MM, WM, or other related disorders is only ~1%. Therefore, most patients with MGUS do not progress to symptomatic MM or other lymphoproliferative disorders.

• #50 Monoclonal Gammopathy of Undetermined Significance (MGUS)—Not So Asymptomatic after All

  https://www.mdpi.com/2072-6694/12/6/1554

  However, even in the absence of malignancy and when matched by age and sex, MGUS patients experience shorter overall survival from diagnosis than is expected (8.1 vs. 12.4 years) according to a prospective cohort study. […] The aim of this review is to examine the most consistently reported co-morbidities associated with MGUS, namely the increased risk of bone fractures, peripheral neuropathy, renal impairment, secondary immunodeficiency, and cardiovascular disease. […] While lytic bone lesions are a defining feature of symptomatic MM, a number of population-based studies have demonstrated an association between MGUS and low bone mineral density/osteoporosis, which, in turn, increases the risk of fractures within, or close to the axial skeleton. […] The occurrence of a non-traumatic fracture in the context of MGUS requires careful assessment by a hematologist with access to cross-sectional imaging and a bone marrow biopsy to exclude a myeloma-defining event.

• #51

  https://haematologica.org/article/view/7062

  The risk of progression for light-chain MGUS is lower when compared to conventional MGUS. […] MGUS patients have a poorer survival than the general population. […] MGUS patients have an increased risk of osteoporosis and fractures (axial distal). […] The M-protein seems to play a role in the development of several skin disorders including plane xanthoma and Schnitzler syndrome. […] The M-protein may act as an anti-platelet autoantibody. […] The M-protein is the direct cause of the kidney disease and these disorders are characterized by the presence of monoclonal deposits in the kidney. […] Importantly, M-protein-associated kidney diseases have a high recurrence rate after kidney transplantation. […] Treatment of M-protein-related disorders is dependent on severity. […] These recommendations are personalized and based on both life expectancy and risk of progression.

• #52 Monoclonal Gammopathy of Undetermined Significance (MGUS)—Not So Asymptomatic after All

  https://www.mdpi.com/2072-6694/12/6/1554

  The term monoclonal gammopathy of renal significance (MGRS) was first introduced in 2012 by the International Kidney and Monoclonal Gammopathy Research Group (IKMG) to describe a set of renal disorders that were characterized by the deposition of monoclonal immunoglobulin in the kidney. […] The most serious complication of MGRS is end-stage renal disease (ESRD) and the comorbidities it entails. […] MGUS is a recognized cause of secondary antibody deficiency. […] The prevalence of MGUS increases with age, as does an age-related decline in immune function, or immunosenescence. […] The majority of patients with MGUS are over the age of 65, and even in healthy individuals, the immune response to vaccination declines with age. […] Cardiovascular Disease (CVD) comprises arterial (coronary, peripheral, and cerebrovascular), venous thromboembolic and structural myocardial disorders. […] Up to 90% of cases of MGUS are undiagnosed and are considered to predate symptomatic MM or lymphoproliferative disease by up to twenty years. […] The identification of MGUS in these scenarios may be coincidental and furthermore, not have an influence over management.

• #53 What is the significance of monoclonal gammopathy of undetermined significance?

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6334115/

  The accumulating evidence around MGUS, its impact on health and the ability to reduce or mitigate health impacts supports the proposal that MGUS fulfils many of the criteria needed to implement a screening programme. […] Monoclonal gammopathy of undetermined significance carries a risk of progression to myeloma and is associated with several complications, including renal impairment, infection and fracture, which can have not only significant morbidity but also potential treatments.

• #54 Risk of MGUS Progression to Myeloma Can Change – NCI

  https://www.cancer.gov/news-events/cancer-currents-blog/2019/mgus-multiple-myeloma-progression-risk

  A new study suggests that a persons risk of progressing from a benign condition called monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma, a type of blood cancer, can change over time. […] Doctors typically estimate a persons risk of progressing soon after MGUS is diagnosed, using a test that measures the amounts of certain markers in the blood. […] The study shows that most of the high-risk patients were low risk at some earlier point, explained lead investigator Ola Landgren, M.D., Ph.D., professor of medicine and chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center. […] Currently, only people who have a high- or intermediate-risk MGUS are recommended to receive annual follow-up tests to check for signs of progression. However, the study investigators said that their findings support annual blood tests for all individuals with MGUS, regardless of their initial risk assessment.

• #55 Monoclonal gammopathy of undetermined significance: A primary care guide | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/86/1/39

  The absence of myeloma-related organ damage particularly osteolytic bone lesions, anemia, otherwise unexplained renal failure, and hypercalcemia is fundamental and necessary for a diagnosis of MGUS. […] Once an M protein is identified, a comprehensive history, physical examination, and laboratory tests (serum protein electrophoresis to quantify the protein, serum immunofixation, serum free light chains, complete blood cell count, calcium, and creatinine) should be done, taking into consideration the differential diagnosis of monoclonal gammopathies discussed above. After MGUS is confirmed, the patient should be risk-stratified to determine the need for bone marrow biopsy and to predict the risk of progression to more serious conditions.

• #56 Risk of MGUS Progression to Myeloma Can Change – NCI

  https://www.cancer.gov/news-events/cancer-currents-blog/2019/mgus-multiple-myeloma-progression-risk

  The findings that low- and intermediate-risk MGUS could convert to high-risk MGUS within a few years, the study authors wrote, supports annual blood testing for all individuals diagnosed with MGUS or light-chain MGUS, as well as yearly assessment of a patients clinical risk status. […] A potential benefit of annual blood testing is that it could lead to earlier detection of multiple myeloma, which could lessen or prevent severe myeloma-related complications like a bone fracture or kidney failure, Dr. Landgren said. […] Drs. Landgren and Hofmann are exploring other markers that may be more predictive of progression to myeloma.

• #57 Monoclonal Gammopathies of Undetermined Significance (MGUS): Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/204297-overview

  The annual risk of progression to multiple myeloma (MM), Waldenstrm macroglobulinemia (WM), amyloidosis (AL), or other lymphoproliferative disorders is approximately 1%. However, the mode and risk of progression vary between IgM MGUS and those with non-IgM MGUS. […] An abnormal serum free light-chain ratio (ratio of kappa to lambda free light chains) and a high serum monoclonal protein (M protein) level (1.5 g per deciliter) are risk factors for progression. […] In a study of 728 Swedish MGUS patients followed for up to 30 years, 84 patients developed a lymphoid disorder, representing a cumulative risk of 15.4%. The 30-year cumulative risk for myeloid malignancies was less than 2%. The 30-year cumulative risk for MM, which occurred in 53 patients, was 10.6%, with an approximately 0.5% annual risk. […] Although autoimmune disease is a well-described risk factor for the development of MGUS, a Swedish population-based study determined that patients with a history of autoimmune disease have a significantly lower risk of progression from MGUS to MM or other lymphoproliferative diseases.

• #58 Monoclonal Gammopathy of Undetermined Significance (MGUS)

  https://www.healthline.com/health/how-serious-is-mgus

  Doctors often recommend monitoring people with MGUS by performing regular blood tests to check for any signs of cancer or disease that may develop over time. […] Each year, the risk of MGUS progressing to multiple myeloma is about 1 percent. […] MGUS is a precancerous condition. Precancerous means that its not cancer, but it has the potential to progress to cancer. Some people with MGUS go on to develop multiple myeloma or other blood cancers, but the majority do not. […] Each year, MGUS has about a 1 percent chance of progressing into multiple myeloma. […] MGUS is a lab finding that may progress into some cancerous conditions. It should be monitored with the help of a physician.

• #59 What is the significance of monoclonal gammopathy of undetermined significance?

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6334115/

  Monoclonal gammopathy of undetermined significance (MGUS) is characterised by the presence of a monoclonal paraprotein in the blood, without the characteristic end organ damage seen in multiple myeloma. […] MGUS has three key diagnostic features: (a) the presence of a monoclonal paraprotein within the serum, at a level 30 g/L; (b) a proliferation of clonal plasma cells within the bone marrow, but forming 10% of the bone marrow; and (c) absence of features of the typical end-organ damage associated with multiple myeloma. […] Population-based screening for MGUS has not been recommended, as advised by the European Myeloma Network and by a joint recommendation from the UK Myeloma Forum and Nordic Myeloma Study Group. […] Currently, there is evidence that MGUS monitoring could lead to improvements in myeloma outcomes, although this evidence is limited.

• #60

  https://www.ashclinicalnews.org/training-education/treat-brief-managing-monoclonal-gammopathy-undetermined-significance/

  Initial screening for monoclonal gammopathy includes serum protein electrophoresis (SPEP), serum immunofixation, and free flightchain (FLC). […] Practice guidelines do not recommend routine screening for MGUS in the general population because of the lack of proven benefit and the absence of curative or preventive therapy. […] Once M-protein is detected, the extent of further evaluation to rule out LPM depends on the pretest probability of the latter and whether clinicians identified an alternative explanation for a patients presenting symptoms. […] To establish an MGUS diagnosis, we generally order the following tests at the time of hematology consult: complete blood count, serum calcium, creatinine, FLC, immunofixation, and 24-hour urine protein electrophoresis. […] There are three subtypes of MGUS, each with distinct criteria for diagnosis.

• #61 Psychological Impact in Individuals with Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma | Published in Clinical Hematology International

  https://chi.scholasticahq.com/article/123608-psychological-impact-in-individuals-with-monoclonal-gammopathy-of-undetermined-significance-and-smoldering-multiple-myeloma

  In our study of 246 newly diagnosed individuals with MGUS or SMM (115 MGUS, 131 SMM), we found that 19% reported anxiety, with no significant difference between the MGUS and SMM groups (22% vs. 17%). […] The diagnosis of MGUS and/or SMM may be linked to psychological effects that can have a detrimental impact on patients quality of life (QoL). […] Our study aimed to evaluate the prevalence of adverse psychosocial effects among individuals with newly diagnosed MGUS and/or SMM. […] Anxiety was found in 19.1% of patients (MGUS: 22% vs. SMM: 17%), while 33.7% had a previous psychiatric disorder which was not different between patients with MGUS vs. SMM. […] Our study found that one third of patients referred with diagnosis of MGUS or SMM has history of psychiatric disorder. This indicates that pre-existing mental health conditions may significantly influence the psychological response of patients upon receiving a diagnosis of MGUS or SMM.

• #62 Psychological Impact in Individuals with Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma | Published in Clinical Hematology International

  https://chi.scholasticahq.com/article/123608-psychological-impact-in-individuals-with-monoclonal-gammopathy-of-undetermined-significance-and-smoldering-multiple-myeloma

  In our study of 246 newly diagnosed individuals with MGUS or SMM (115 MGUS, 131 SMM), we found that 19% reported anxiety, with no significant difference between the MGUS and SMM groups (22% vs. 17%). […] The diagnosis of MGUS and/or SMM may be linked to psychological effects that can have a detrimental impact on patients quality of life (QoL). […] Our study aimed to evaluate the prevalence of adverse psychosocial effects among individuals with newly diagnosed MGUS and/or SMM. […] Anxiety was found in 19.1% of patients (MGUS: 22% vs. SMM: 17%), while 33.7% had a previous psychiatric disorder which was not different between patients with MGUS vs. SMM. […] Our study found that one third of patients referred with diagnosis of MGUS or SMM has history of psychiatric disorder. This indicates that pre-existing mental health conditions may significantly influence the psychological response of patients upon receiving a diagnosis of MGUS or SMM.

• #63 Psychological Impact in Individuals with Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma | Published in Clinical Hematology International

  https://chi.scholasticahq.com/article/123608-psychological-impact-in-individuals-with-monoclonal-gammopathy-of-undetermined-significance-and-smoldering-multiple-myeloma

  The study underscores the importance of adopting a holistic approach to patient care, highlighting the need to address both the medical and psychological dimensions of managing MGUS and SMM. […] Given that anxiety can negatively affect patients well-being and quality of life, healthcare providers should prioritize comprehensive care that includes addressing and managing anxiety alongside the medical aspects of the disease. […] This practice provides physicians with essential information, facilitating the delivery of optimal care.

• #64 Ask the Nurse: monoclonal gammopathy of undetermined significance (MGUS) – Myeloma UK

  https://www.myeloma.org.uk/library/ask-the-nurse-mgus/

  For most patients, a diagnosis of monoclonal gammopathy of undetermined significance (MGUS) does not affect their daily life. However, it can be concerning to receive a diagnosis for which there is no treatment, that requires regular monitoring, and has a very small possibility of developing into another condition. […] MGUS is often only diagnosed when tests are performed to investigate other problems. […] Most MGUS patients have a stable condition that does not affect their general health. […] As an MGUS patient, you will have regular check-ups and blood tests because a very small proportion of patients will develop a more serious condition, such as myeloma, AL amyloidosis or lymphoma. […] Typically, MGUS is actively monitored with blood tests but not treated. […] Currently, there are no specific treatments to stop MGUS from progressing. However, this is a focus area for our research. […] Unfortunately, doctors do not know why some people with MGUS develop cancer, and others do not. […] Talk to your doctor or nurse about your concerns. They can explain more about your condition and risk and arrange counselling for you if needed.

• #65

  https://www.ashclinicalnews.org/training-education/treat-brief-managing-monoclonal-gammopathy-undetermined-significance/

  Any concern for progression should prompt additional testing, such as imaging studies or BM or tissue biopsy. […] The potential harms associated with an MGUS diagnosis are rarely a topic of doctors office conversation or even academic debate. […] The cost of MGUS follow-up estimated to be more than $100 million annually in the U.S. is substantial and cannot be ignored. […] We expect that the number of Americans living with a diagnosis of MGUS will rise from approximately 500,000 to well over one million in the next 30 years, yet there is surprisingly limited evidence to inform best clinical practice for the extent of initial evaluation and subsequent followup care.

• #66 Prognosis of young patients with monoclonal gammopathy of undetermined significance (MGUS) | Blood Cancer Journal

  https://www.nature.com/articles/s41408-021-00406-6

  Young patients with MGUS have a similar risk of progression as in older patients, 1.4% per year. […] When occurring in the setting of immune-related disorders, the M protein is smaller, more likely to resolve, and may have a lower risk of progression than in patients in whom MGUS is detected without concurrent immune-related disorder.

• #67 Geographic Prevalence Patterns and Modifiable Risk Factors for Monoclonal Gammopathy of Undetermined Significance

  https://www.mdpi.com/2673-6357/4/4/27

  In this systematic review, we outline original research on the prevalence and risk factors for MGUS across geographic locations to gain further insight into the potential potency of sociocultural influences, lifestyle factors, medical conditions, and environmental exposures as risk factors for MGUS. We noted that the prevalence of MGUS is highly varied. Population-based screening studies provide the most accurate geographic prevalence estimates, while studies from hospital and outpatient settings tend to overestimate MGUS prevalence. […] Overall, the relationship between MGUS and the aforementioned risk factors is still poorly understood. However, the data summarized in this review support the notion that the etiology of MGUS and progressive clonal proliferation of plasma cells may be linked to chronic antigen stimulation and genomic aberrations triggered by infectious organisms, chronic inflammation, autoantigens, lifestyle factors, and environmental exposures.

• #68 Risk of MGUS Progression to Myeloma Can Change – NCI

  https://www.cancer.gov/news-events/cancer-currents-blog/2019/mgus-multiple-myeloma-progression-risk

  The findings that low- and intermediate-risk MGUS could convert to high-risk MGUS within a few years, the study authors wrote, supports annual blood testing for all individuals diagnosed with MGUS or light-chain MGUS, as well as yearly assessment of a patients clinical risk status. […] A potential benefit of annual blood testing is that it could lead to earlier detection of multiple myeloma, which could lessen or prevent severe myeloma-related complications like a bone fracture or kidney failure, Dr. Landgren said. […] Drs. Landgren and Hofmann are exploring other markers that may be more predictive of progression to myeloma.

• #69 Changing paradigms in diagnosis and treatment of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) | Leukemia

  https://www.nature.com/articles/s41375-020-01051-x

  Multiple myeloma (MM) is a highly heterogenous disease that exists along a continuous disease spectrum starting with premalignant conditions monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) that inevitably precede MM. […] In this review, we discuss the epidemiology of MGUS and SMM and current models for risk stratification that predict MGUS and SMM progression to MM. […] We further discuss genetic heterogeneity and clonal evolution in MM and the interplay between tumor cells and the bone marrow (BM) microenvironment. […] Finally, we provide an overview of the current recommendations for the management of MGUS and SMM and discuss the open controversies in the field in light of promising results from early intervention clinical trials. […] Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study.

• #70 Prognosis of young patients with monoclonal gammopathy of undetermined significance (MGUS) | Blood Cancer Journal

  https://www.nature.com/articles/s41408-021-00406-6

  Our study explored the prognosis of MGUS in 249 patients younger than 40 years of age. […] The risk of progression to plasma cell or lymphoid disorders in young patients was predicted by the size of the serum M protein, a potent risk factor with a 3 fold higher risk of progression per unit increase. […] Our study did not find a statistically significant difference in the risk of progression between patients with immune-related conditions and patients without immune-related conditions, although there was a trend towards higher risk of progression in those without a coexisting immune disorder (HR 2.36, 95% CI 0.856.52, p=0.088). […] The size of M protein in our study is relatively small compared to those in previous studies. […] The long-term prognosis of transient paraproteinemia is worth investigation.

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