Monoclonal Gammopathy of Undetermined Significance and Smoldering Myeloma

Monoclonal gammopathy of undetermined significance (MGUS) is a finding on a blood test, not an illness with symptoms. One family of plasma cells — the antibody-making white cells that live in the bone marrow — has copied itself into a small clone, and that clone releases a single, identical antibody protein called a monoclonal protein. In monoclonal gammopathy of undetermined significance the clone is small and causes no organ damage. Smoldering multiple myeloma is the next step along the same road: the clone is larger, but it still causes none of the organ damage that defines active multiple myeloma. This page sets out how often these findings turn up, how they are measured, how researchers estimate the chance of progression, what the trials of early treatment found, which follow-up schedules expert panels describe, and what is still unknown. The main disease is covered on the Multiple Myeloma page.

Table of Contents

  1. What the Two Conditions Are
  2. How Often the Finding Turns Up With Age
  3. How the Monoclonal Protein Is Found
  4. Where the Lines Are Drawn: The 2014 Definitions
  5. The Stage That Comes Before Myeloma
  6. The Minnesota Cohort: 34 Years of Follow-Up
  7. Sorting Risk: The Mayo Clinic Model
  8. Light-Chain Monoclonal Gammopathy
  9. Risks That Do Not Depend on Progression
  10. When a Small Clone Damages Organs
  11. Smoldering Myeloma: Its Course and the Risk Models
  12. Screening a Whole Country: The iStopMM Study
  13. Trials of Early Treatment for Smoldering Myeloma
  14. What the US Drug Labels Say
  15. Follow-Up Schedules Described by Expert Panels
  16. What Is Not Known
  17. Key Research Papers
  18. Connections
  19. Featured Videos

What the Two Conditions Are

Every antibody is built from two heavy chains and two light chains. Heavy chains come in types named G, A, M, D and E, which is where the names immunoglobulin G, immunoglobulin A and immunoglobulin M come from; light chains come in two types, kappa and lambda. A healthy immune system makes millions of slightly different antibodies at once. When one clone of plasma cells grows out of proportion, its single antibody shows up in the blood as a sharp excess of one protein — the monoclonal protein, sometimes called a paraprotein or an “M spike”.

A 2018 review in the journal Blood describes three situations behind a monoclonal protein. It can signal active multiple myeloma or another lymphoid cancer that needs treatment straight away. More often it comes from a small or quiet clone that is completely asymptomatic and, in the review’s words, requires regular monitoring only — this is monoclonal gammopathy of undetermined significance. And sometimes a quiet clone that needs no treatment as a cancer still damages organs through the toxicity of its protein (Fermand 2018).

Smoldering multiple myeloma is described by the International Myeloma Working Group as an asymptomatic precursor state of multiple myeloma (Mateos 2020). The Mayo Clinic’s 2007 series calls it an asymptomatic plasma-cell disorder with a high risk of progression to symptomatic multiple myeloma or amyloidosis (Kyle 2007). The difference between the two precursor states is one of size: how much monoclonal protein is in the blood and how much of the bone marrow is made up of plasma cells.

How Often the Finding Turns Up With Age

The most complete count comes from Olmsted County, Minnesota. Researchers identified every living resident aged 50 or older as of January 1, 1995, and tested serum left over from routine clinical blood tests, or asked people for a sample when none was available. They obtained serum from 21,463 of the 28,038 residents aged 50 or older (76.6 percent) (Kyle 2006).

That count used the standard protein tests, which detect a whole antibody. When the same Olmsted County samples were later run through the serum free light chain test as well, the light-chain-only form of the condition added a prevalence of 0.8 percent, bringing the overall prevalence to 4.2 percent (Dispenzieri 2010; see the light-chain section below). A 2024 review puts the prevalence of monoclonal proteins in the United States at around 5 percent and notes that the incidence rises with age (Schmidt 2024).

In Iceland, where everyone aged 40 or older was invited to be screened (see the iStopMM section), 3,541 of the 75,422 people screened had monoclonal gammopathy of undetermined significance and entered the follow-up trial (Rögnvaldsson 2026).

How the Monoclonal Protein Is Found

Because it causes no symptoms of its own, the finding comes to light only when someone tests the blood for it. Three laboratory tests do most of the work.

Serum protein electrophoresis. A drop of serum is placed on a gel and an electric current pulls the proteins apart by size and charge. Normal antibodies spread out into a broad smear; a monoclonal protein, because every copy is identical, travels as one narrow band. In the Olmsted County survey, agarose-gel electrophoresis was run on every sample (Kyle 2006). The size of the band gives the monoclonal protein level, the number most risk models use.

Immunofixation. Any sample with a discrete band, or a band suspected to be there, went on to immunofixation (Kyle 2006). This test identifies the type of the monoclonal protein — which heavy chain (G, A or M) and which light chain (kappa or lambda) it carries. The type matters: an immunoglobulin M protein points toward lymphoma-type disorders such as Waldenström’s macroglobulinemia, while other types point toward myeloma.

The serum free light chain test. Plasma cells make slightly more light chains than they need, and the spare ones circulate freely. This blood test measures free kappa and free lambda light chains and the ratio between them. In the Mayo Clinic analysis, a kappa-to-lambda ratio below 0.26 or above 1.65 was counted as abnormal (Rajkumar 2005). A clone that makes only light chains can be invisible on ordinary electrophoresis but shows up as an abnormal ratio; that is how the light-chain-only form of the condition was defined (Dispenzieri 2010).

The same set of tests appears in other settings. An international kidney consensus lists serum and urine protein electrophoresis and immunofixation, plus serum free light chains, as the way to identify the monoclonal protein when a kidney disorder is suspected (Leung 2019). The site’s Immunoglobulins page explains the antibody blood tests in more detail.

Where the Lines Are Drawn: The 2014 Definitions

In 2014 the International Myeloma Working Group updated the definition of multiple myeloma. Before that, myeloma required organ damage known as the “CRAB” features: high blood calcium, kidney failure, anemia (too few red blood cells) and bone lesions. The 2014 update added validated biomarkers linked to near-inevitable development of those features in people who would otherwise have been labelled as having smoldering myeloma. The working group judged that delaying the myeloma label, and with it treatment, could be harmful for these patients (Rajkumar 2014).

The three biomarkers, as summarised by a later Mayo Clinic study, are bone marrow plasma cells of 60 percent or more, a serum free light chain ratio of 100 or more, or more than one focal lesion on magnetic resonance imaging (Lakshman 2018). Anyone meeting one of them is now classed as having multiple myeloma, not smoldering myeloma.

That leaves three tiers:

The working group asked that future studies look for any differences in outcome caused by the new definition (Rajkumar 2014). Because the 2014 change moved people with these biomarkers out of the smoldering group, smoldering cohorts collected before 2014 may include people who would now be diagnosed with myeloma, and new risk models were built on patients meeting the revised criteria (Lakshman 2018; Mateos 2020).

The Stage That Comes Before Myeloma

For years it was not known whether every case of myeloma passes through a silent precursor stage. A study inside the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which enrolled 77,469 healthy adults across the United States and stored their blood, answered that question. Seventy-one participants later developed multiple myeloma, and up to six stored samples taken 2 to 9.8 years before each diagnosis were tested (Landgren 2009).

A monoclonal gammopathy was present in 100.0 percent of them 2 years before diagnosis, 98.3 percent at 3 years, 97.9 percent at 4 years, 94.6 percent at 5 years, 100.0 percent at 6 years, 93.3 percent at 7 years and 82.4 percent 8 or more years before diagnosis. In about half of these people the monoclonal protein level and the abnormal light chain ratio rose year by year before myeloma appeared. The authors concluded that an asymptomatic stage consistently preceded myeloma, and that new molecular markers are needed to predict who will progress (Landgren 2009).

The reverse is not true: most people with monoclonal gammopathy of undetermined significance never develop myeloma, as the long Minnesota follow-up below shows.

The Minnesota Cohort: 34 Years of Follow-Up

The longest record of what happens to people with this finding comes from the Mayo Clinic. Researchers identified 1,384 residents of southeastern Minnesota whose monoclonal gammopathy of undetermined significance was diagnosed at the clinic from 1960 through 1994, and followed them for decades.

The 2002 report. Over 11,009 person-years of follow-up, the finding progressed in 115 of the 1,384 patients to multiple myeloma, immunoglobulin M lymphoma, primary amyloidosis, macroglobulinemia, chronic lymphocytic leukemia or plasmacytoma. Compared with the white population of the Iowa cancer registry, the overall relative risk of progression was 7.3. For the separate outcomes the relative risk was 25.0 for multiple myeloma, 2.4 for immunoglobulin M lymphoma, 8.4 for primary amyloidosis, 46.0 for macroglobulinemia, 0.9 for chronic lymphocytic leukemia and 8.5 for plasmacytoma. In 32 more patients the monoclonal protein climbed above 3 g per deciliter or the marrow plasma cells above 10 percent — smoldering myeloma — without progression to overt disease. The cumulative probability of progression was 12 percent at 10 years, 25 percent at 20 years and 30 percent at 25 years. The starting level of the monoclonal protein was a significant predictor of progression at 20 years, and the authors summarised the risk as about 1 percent per year (Kyle 2002).

The 2018 report. The same cohort was reported again after a median follow-up of 34.1 years (range 0.0 to 43.6 years) and 14,130 person-years. By then the finding had progressed in 147 patients (11 percent), a rate 6.5 times that of the control population. Without accounting for deaths from other causes, the risk of progression was 10 percent at 10 years, 18 percent at 20 years, 28 percent at 30 years, 36 percent at 35 years and 36 percent at 40 years (Kyle 2018).

The two reports give different percentages for the same cohort at the same time points. The 2018 abstract states that its figures were calculated without accounting for death from competing causes; the 2002 abstract does not describe its method in those terms. Both are reproduced here as each paper gives them.

The 2018 report also found that people with the finding lived shorter lives than expected: median survival was 8.1 years, against 12.4 years in Minnesota residents of matched age and sex (Kyle 2018). The abstract does not say how much of the gap comes from the clone itself.

Sorting Risk: The Mayo Clinic Model

Because most people with the finding never progress, researchers looked for features that separate the few who do. In the Minnesota cohort, serum taken within 30 days of diagnosis was available for 1,148 of the 1,384 patients. At a median follow-up of 15 years, 87 of them (7.6 percent) had progressed to a malignancy. An abnormal free light chain ratio (below 0.26 or above 1.65) was found in 379 patients (33 percent), and their risk of progression was higher, with a hazard ratio of 3.5, independent of the size and type of the monoclonal protein (Rajkumar 2005). A hazard ratio compares how often an event happens in one group with how often it happens in another over the same period; 1 means no difference.

Three risk factors were combined into a model:

The 20-year risk of progression was 58 percent with all three (high risk), 37 percent with any two (high-intermediate risk), 21 percent with one (low-intermediate risk) and 5 percent with none (low risk) (Rajkumar 2005).

The 34-year report refined the picture by splitting immunoglobulin M from the other types. Using two risk factors — an abnormal free light chain ratio and a monoclonal protein of 1.5 g per deciliter or more — the 20-year risk of progression for the immunoglobulin M type was 55 percent with both factors, 41 percent with one and 19 percent with neither. For all other types it was 30 percent with both, 20 percent with one and 7 percent with neither (Kyle 2018). The authors noted significant differences in risk between the immunoglobulin M type and the rest.

A 2010 International Myeloma Working Group consensus describes low-risk monoclonal gammopathy of undetermined significance as a monoclonal protein below 15 g per liter, of the immunoglobulin G type, with a normal free light chain ratio (Kyle 2010).

Light-Chain Monoclonal Gammopathy

The classic form of the condition is defined by a whole antibody with a heavy chain, and it is the precursor of 80 percent of multiple myeloma cases. The other 20 percent of myeloma cases make no heavy chain at all — only light chains — and a Mayo Clinic team set out to find the matching precursor (Dispenzieri 2010).

They ran the serum free light chain test on the stored Olmsted County samples. Of 18,357 people tested, 610 (3.3 percent) had an abnormal free light chain ratio. In 213 of them a whole antibody was present, which meant the classic form. Of the remaining 397, 146 also had a raised level of at least one free light chain and met the definition of light-chain monoclonal gammopathy of undetermined significance (Dispenzieri 2010).

The kidney finding links this form to the “clinical significance” disorders below. A light chain is also the building block of the deposits in AL amyloidosis, which the 2002 Minnesota report lists among the outcomes of progression (Kyle 2002).

Risks That Do Not Depend on Progression

Two studies using population-based data from Sweden compared 5,326 people diagnosed with monoclonal gammopathy of undetermined significance between 1958 and 2006 with 20,161 matched controls. They found two risks that appear even when the clone never becomes a cancer.

Fractures. People with the finding had a higher risk of any fracture at 5 years (hazard ratio 1.74) and at 10 years (hazard ratio 1.61). The excess was greater for fractures of the spine, pelvis, skull, breastbone and ribs than for arm and leg fractures. Over 10 years the hazard ratio was 2.37 for spine or pelvis fractures, 1.93 for breastbone or rib fractures, 1.23 for arm fractures, 1.40 for leg fractures and 4.25 for other or multiple fractures. The risk did not differ by protein type or level, and people who had fractures did not go on to more myeloma or Waldenström’s macroglobulinemia. The authors read this as a sign that bone changes begin early in the development of myeloma (Kristinsson 2010).

Infections. In the same Swedish population, people with the finding had a twofold higher risk of developing any infection at 5 and 10 years. The excess covered bacterial infections — pneumonia, bone infection, blood infection, kidney infection, skin infection, heart-valve infection and meningitis — and viral infections (influenza and shingles). The risk was highest when the monoclonal protein was above 2.5 g per deciliter at diagnosis, but it was raised even below 0.5 g per deciliter. People who developed infections did not go on to more myeloma or related cancers (Kristinsson 2012).

These are observational studies: they show an association, not proof that the clone causes the fractures or infections.

When a Small Clone Damages Organs

The words “undetermined significance” assume the protein is harmless. Sometimes it is not. A 2018 review proposed the umbrella term monoclonal gammopathy of clinical significance for disorders in which a small, quiet B-cell clone that would not need treatment as a cancer still causes potentially severe organ damage, through the toxicity of its protein or other mechanisms. The authors describe these disorders as increasingly observed but still poorly recognised and frequently undertreated, and note that controlling the clone usually leads to organ improvement (Fermand 2018). Two conditions in this family with their own pages are POEMS syndrome and cryoglobulinemia.

The kidney is the organ most studied. The International Kidney and Monoclonal Gammopathy Research Group introduced the term monoclonal gammopathy of renal significance in 2012 and refined it in 2017: a clonal disorder that produces a monoclonal protein toxic to the kidney but does not meet the blood-cancer criteria for treatment of a specific malignancy. Its 2019 consensus report states that the diagnosis is established by kidney biopsy, with immunofluorescence to show the deposits, and that the group recommends a kidney biopsy when the condition is suspected. It lists serum and urine protein electrophoresis, immunofixation and serum free light chains to identify the protein, and a bone marrow biopsy to identify the clone. The report did not address treatment (Leung 2019).

Smoldering Myeloma: Its Course and the Risk Models

The 2007 Mayo Clinic series. Researchers reviewed every Mayo Clinic patient who met the working group’s criteria for smoldering myeloma between 1970 and 1995 — 276 people. Over 2,131 person-years, symptomatic multiple myeloma or amyloidosis developed in 163 (59 percent). The risk of progression was 10 percent per year for the first 5 years, about 3 percent per year for the next 5 years and 1 percent per year for the last 10 years; the cumulative probability of progression was 73 percent at 15 years. The share of plasma cells in the marrow and the serum monoclonal protein level were combined into a model with three prognostic groups (Kyle 2007). This series predates the 2014 definitions, so it may include people who would now be diagnosed with myeloma.

The Mayo “20/2/20” model. After the 2014 change, a Mayo Clinic team studied 421 patients with smoldering myeloma diagnosed between 2003 and 2015. Median time to progression was 57 months. Three factors independently predicted faster progression (Lakshman 2018):

Median time to progression was 110 months with none of these factors (143 patients, low risk), 68 months with one (121 patients, intermediate risk) and 29 months with two or more (153 patients, high risk). Age and lowered normal antibodies were not significant (Lakshman 2018).

The International Myeloma Working Group “2/20/20” model. The working group pooled 1,996 patients meeting the revised criteria and found the same three factors, here measured against the risk of progression within 2 years: a monoclonal protein above 2 g per deciliter (hazard ratio 2.1), a free light chain ratio above 20 (hazard ratio 2.7) and marrow plasma cells above 20 percent (hazard ratio 2.4) (Mateos 2020).

Adding chromosome changes in the plasma cells — t(4;14), t(14;16), gain of 1q and/or deletion of 13q — split patients into four groups with 2-year progression risks of 6, 23, 46 and 63 percent (Mateos 2020).

Screening a Whole Country: The iStopMM Study

The Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM) is the first population-based screening study for the condition that also randomly assigns people to different follow-up strategies. Icelandic residents born before 1976 were offered participation; of the 148,704 people in the target population, 80,759 (54.3 percent) gave consent. People found to have the condition were randomly assigned to three arms: arm 1 was not contacted, arm 2 was followed according to current guidelines, and arm 3 was followed more intensively. Participants who progressed were offered early treatment (Rögnvaldsson 2021).

How common smoldering myeloma turned out to be. Of the 80,759 who consented, 75,422 (93 percent) were screened. The prevalence of smoldering myeloma was 0.53 percent in people aged 40 or older — 0.67 percent in men and 0.39 percent in women — and it rose with age in both sexes. The 193 people found had a median age of 70 (range 44 to 92) and 60 percent were men. Their mean monoclonal protein was 0.62 g per deciliter, and 73 percent had 11 to 20 percent plasma cells in the marrow. The authors noted that this high prevalence matters for future treatment policy as evidence for treatment at the smoldering stage emerges (Thorsteinsdóttir 2023).

What screening and follow-up changed. The 3,541 people with monoclonal gammopathy of undetermined significance were split between no notification and the two follow-up arms. After a median follow-up of 4.5 years (Rögnvaldsson 2026):

The authors state that longer follow-up is needed to learn whether screening affects survival and whether it is cost-effective (Rögnvaldsson 2026).

Trials of Early Treatment for Smoldering Myeloma

The authors of the lenalidomide trials describe observation until symptoms develop as the standard of care for smoldering myeloma. Three randomised trials tested whether starting treatment earlier changes the outcome.

The Spanish lenalidomide and dexamethasone trial (QuiRedex). This phase 3 trial randomly assigned 119 patients with high-risk smoldering myeloma to treatment or observation. The trial gave lenalidomide 25 mg a day on days 1 to 21 plus dexamethasone 20 mg a day on days 1 to 4 and 12 to 15, in 4-week cycles for nine cycles, followed by lenalidomide 10 mg a day on days 1 to 21 of each 28-day cycle for 2 years. After a median of 40 months, the median time to progression had not been reached in the treatment group against 21 months with observation (hazard ratio 0.18). Three-year survival was 94 percent against 80 percent (hazard ratio for death 0.31). A partial response or better was seen in 79 percent after induction and 90 percent during maintenance, and toxic effects were mainly grade 2 or lower (Mateos 2013). After a median of 12.5 years, the median time to progression was 9.5 years with treatment against 2.1 years with observation (hazard ratio 0.28), and median overall survival was not reached with treatment against 8.5 years with observation (hazard ratio 0.57). Patients who progressed received standard treatment, and survival measured from progression was comparable in both arms (Mateos 2022).

The US lenalidomide trial (E3A06). This trial randomly assigned 182 patients with intermediate- or high-risk smoldering myeloma to lenalidomide alone (92 patients) or observation (90 patients). The trial gave lenalidomide 25 mg by mouth on days 1 to 21 of a 28-day cycle. Progression here required organ damage from myeloma as well as a rise in the blood markers. At a median follow-up of 35 months, 50 percent responded to lenalidomide and no one in the observation arm responded. Progression-free survival was longer with lenalidomide (hazard ratio 0.28): 98, 93 and 91 percent at 1, 2 and 3 years, against 89, 76 and 66 percent with observation. Only six deaths had been reported, two with lenalidomide and four with observation (hazard ratio 0.46, with a wide 95 percent confidence interval of 0.08 to 2.53). Grade 3 or 4 side effects other than blood-count changes occurred in 25 patients (28 percent) taking lenalidomide (Lonial 2020).

The daratumumab trial (AQUILA). Daratumumab is an antibody against a protein called CD38 on plasma cells. This phase 3 trial randomly assigned 390 patients with high-risk smoldering myeloma to daratumumab injected under the skin (194 patients) or active monitoring (196 patients). Treatment continued for 39 cycles, for 36 months, or until progression was confirmed, whichever came first. Progression to active myeloma was judged by an independent committee using the working group’s criteria (Dimopoulos 2025).

What the US Drug Labels Say

Daratumumab and hyaluronidase-fihj (the under-the-skin form). The current US label on DailyMed (revised January 2026) lists, among its uses, treatment on its own for adults with high-risk smoldering multiple myeloma. It states that the drug is indicated only for high-risk smoldering myeloma and not for other risk categories. In AQUILA, as the label reports, 41 percent of patients had two or more of the three high-risk features (a monoclonal protein above 2 g per deciliter, a free light chain ratio above 20 and marrow plasma cells above 20 percent). The trial’s patients had a median age of 64 (range 31 to 86); 48 percent were men, and 83 percent were White, 8 percent Asian and 3 percent Black or African American.

The label gives 1,800 mg of daratumumab with 30,000 units of hyaluronidase, injected under the skin over about 3 to 5 minutes: weekly in weeks 1 to 8, every 2 weeks in weeks 9 to 24, and every 4 weeks from week 25 until a diagnosis of multiple myeloma or a maximum of 3 years.

Safety figures the label reports from AQUILA:

Across a pooled group of 1,639 patients treated with the drug for several conditions, the label reports serious infections in 24 percent and fatal infections in 2.5 percent. It also notes that there were too few patients aged 75 or older in AQUILA to judge whether the drug works differently in them.

Lenalidomide. The US label on DailyMed does not list smoldering myeloma among its uses; its myeloma uses are multiple myeloma in combination with dexamethasone and maintenance after a stem cell transplant. It carries a boxed warning for harm to an unborn baby, for low neutrophil and platelet counts, and for blood clots in veins and arteries, and it is available only through a restricted distribution program because of the risk to pregnancy.

Follow-Up Schedules Described by Expert Panels

The 2010 International Myeloma Working Group consensus describes follow-up by risk group (Kyle 2010):

The same consensus gives the risk of progression of monoclonal gammopathy of undetermined significance as about 1 percent per year, and that of smoldering myeloma as 10 percent per year for the first 5 years, 3 percent per year for the next 5 years and 1 to 2 percent per year for the following 10 years (Kyle 2010). These schedules predate the 2014 definitions and the Icelandic trial.

The Icelandic trial is the first randomised test of follow-up itself. Guideline-based and more intensive follow-up found smoldering myeloma far more often and found active disease a year earlier, with fewer people arriving with symptoms, but did not change the rate of active myeloma over 4.5 years (Rögnvaldsson 2026). Decisions about testing and follow-up for any one person belong with a clinician.

The signs that mark the move to active myeloma are the CRAB features listed above — high blood calcium, kidney failure, anemia and bone lesions (Rajkumar 2014) — and the higher rates of fractures and infections described earlier were found in people with the precursor finding itself (Kristinsson 2010; Kristinsson 2012).

What Is Not Known

Key Research Papers

  1. Kyle RA, Larson DR, Therneau TM, Dispenzieri A, Kumar S, Cerhan JR, Rajkumar SV. Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance. N Engl J Med. 2018;378(3):241-249. PubMed PMID: 29342381
  2. Kyle RA, Therneau TM, Rajkumar SV, Offord JR, Larson DR, Plevak MF, Melton LJ 3rd. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med. 2002;346(8):564-9. PubMed PMID: 11856795
  3. Kyle RA, Therneau TM, Rajkumar SV, Larson DR, Plevak MF, Offord JR, et al. Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med. 2006;354(13):1362-9. PubMed PMID: 16571879
  4. Rajkumar SV, Kyle RA, Therneau TM, Melton LJ 3rd, Bradwell AR, Clark RJ, et al. Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005;106(3):812-7. PubMed PMID: 15855274
  5. Dispenzieri A, Katzmann JA, Kyle RA, Larson DR, Melton LJ 3rd, Colby CL, et al. Prevalence and risk of progression of light-chain monoclonal gammopathy of undetermined significance: a retrospective population-based cohort study. Lancet. 2010;375(9727):1721-8. PubMed PMID: 20472173
  6. Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009;113(22):5412-7. PubMed PMID: 19179464
  7. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-48. PubMed PMID: 25439696
  8. Kyle RA, Durie BG, Rajkumar SV, Landgren O, Blade J, Merlini G, et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010;24(6):1121-7. PubMed PMID: 20410922
  9. Kyle RA, Remstein ED, Therneau TM, Dispenzieri A, Kurtin PJ, Hodnefield JM, et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. N Engl J Med. 2007;356(25):2582-90. PubMed PMID: 17582068
  10. Lakshman A, Rajkumar SV, Buadi FK, Binder M, Gertz MA, Lacy MQ, et al. Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria. Blood Cancer J. 2018;8(6):59. PubMed PMID: 29895887
  11. Mateos MV, Kumar S, Dimopoulos MA, González-Calle V, Kastritis E, Hajek R, et al. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J. 2020;10(10):102. PubMed PMID: 33067414
  12. Mateos MV, Hernández MT, Giraldo P, de la Rubia J, de Arriba F, López Corral L, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013;369(5):438-47. PubMed PMID: 23902483
  13. Mateos MV, Hernández MT, Salvador C, Rubia J, de Arriba F, López-Corral L, et al. Lenalidomide-dexamethasone versus observation in high-risk smoldering myeloma after 12 years of median follow-up time: A randomized, open-label study. Eur J Cancer. 2022;174:243-250. PubMed PMID: 36067617
  14. Lonial S, Jacobus S, Fonseca R, Weiss M, Kumar S, Orlowski RZ, et al. Randomized Trial of Lenalidomide Versus Observation in Smoldering Multiple Myeloma. J Clin Oncol. 2020;38(11):1126-1137. PubMed PMID: 31652094
  15. Dimopoulos MA, Voorhees PM, Schjesvold F, Cohen YC, Hungria V, Sandhu I, et al. Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma. N Engl J Med. 2025;392(18):1777-1788. PubMed PMID: 39652675
  16. Rögnvaldsson S, Love TJ, Thorsteinsdottir S, Reed ER, Óskarsson JÞ, Pétursdóttir Í, et al. 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 J. 2021;11(5):94. PubMed PMID: 34001889
  17. Thorsteinsdóttir S, Gíslason GK, Aspelund T, Rögnvaldsson S, Óskarsson JÞ, Sigurðardóttir GÁ, et al. Prevalence of smoldering multiple myeloma based on nationwide screening. Nat Med. 2023;29(2):467-472. PubMed PMID: 36747117
  18. Rögnvaldsson S, Thorsteinsdóttir S, Eythorsson E, Wessman ID, Sigurdardottir GA, Vidarsson B, et al. Clinical and Psychological Outcomes After Monoclonal Gammopathy Screening: A Population-Based Screening Study and Subsequent Randomized Trial of Follow-Up. J Clin Oncol. 2026;44(29):2781-2786. PubMed PMID: 42447419
  19. Leung N, Bridoux F, Batuman V, Chaidos A, Cockwell P, D'Agati VD, et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group. Nat Rev Nephrol. 2019;15(1):45-59. PubMed PMID: 30510265
  20. Fermand JP, Bridoux F, Dispenzieri A, Jaccard A, Kyle RA, Leung N, Merlini G. Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications. Blood. 2018;132(14):1478-1485. PubMed PMID: 30012636
  21. Kristinsson SY, Tang M, Pfeiffer RM, Björkholm M, Blimark C, Mellqvist UH, et al. Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study. Blood. 2010;116(15):2651-5. PubMed PMID: 20610813
  22. Kristinsson SY, Tang M, Pfeiffer RM, Björkholm M, Goldin LR, Blimark C, et al. Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study. Haematologica. 2012;97(6):854-8. PubMed PMID: 22180421
  23. Schmidt T, Gahvari Z, Callander NS. SOHO State of the Art Updates and Next Questions: Diagnosis and Management of Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2024;24(10):653-664. PubMed PMID: 38641486

PubMed Topic Searches

  1. Monoclonal gammopathy of undetermined significance: progression
  2. Smoldering multiple myeloma: risk stratification
  3. Smoldering multiple myeloma: randomised trials of early treatment
  4. Light-chain monoclonal gammopathy of undetermined significance
  5. Monoclonal gammopathy of renal significance
  6. The iStopMM screening study

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