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Natural History Study of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM)

18 Years
Open (Enrolling)
Smoldering Myeloma, Monoclonal Gammopathy of Undetermined Significance

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Trial Information

Natural History Study of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM)


- Multiple Myeloma (MM) is an incurable plasma cell neoplasm with a median survival of
3-4 years.

- Monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM)
are premalignant plasma cell proliferative disorders characterized by elevated
monoclonal protein and bone marrow plasma cells. MGUS affects 3.2% of Caucasians over
the age of 50 and has a 1% annual risk of progression to MM. approximately 3000 cases
of SMM are diagnosed annually with a 10% annual risk of progression to MM.

- Current risk stratification schemes rely on serum protein markers and phenotyping by
flow cytometry. While they can differentiate high and low risk patients, they cannot
predict outcome for individual patients, are not integrated with one another, and have
limited direct correlation to biology.

- Paired samples linked to clinical information can advance research into improved risk
stratification, the pathogenesis of MGUS, SMM, and MM, and the potential for an early
treatment window for these incurable diseases.


- To characterize the natural history and prognosis of MGUS and SMM

- To integrate protein markers (including immunoglobulin free light-chains) and
immunophenotyping by flow cytometry with molecular profiles (including gene expression
profiles) and clinical outcomes

- To apply expertise and diagnostic technology to provide improved evaluation,
monitoring, and risk-stratification for patients on this protocol

- To provide paired samples of blood and tissue linked to clinical and molecular
information for pilot translational studies


- A confirmed diagnosis of MGUS or SMM (based on IMWG diagnostic criteria)

- Age greater than or equal to 18 years

- ECOG performance status in the range of 0-2

- Patients who have a diagnosis of MM are not eligible for this study.


- This is a prospective cohort study of patients with either MGUS or SMM.

- Following initial evaluation and confirmation of diagnosis, patients will be followed
as clinically indicated, usually at 12 month intervals.

- The primary endpoint is progression to MM requiring treatment.

- The minimum length of follow up will be 5 years.

- Patients may donate cellular products or tissues as appropriate for research purposes.

154 patients with MGUS and 154 patients with SMM will be enrolled on this protocol.

Inclusion Criteria


- Diagnosis of MGUS and SMM will be made in accordance with the clinical diagnostic
criteria set forth by the International Myeloma Working Group (Table 1).

- The diagnoses will be confirmed by either serum/urine protein electrophoresis,
immunofixation and light-chain assays; or immunohistochemistry analyses of the bone
marrow biopsy, or a combination of these tests.

- Age greater than or equal to 18 years.

- ECOG performance status of 0-2.

- The patient must be competent to sign an informed consent form.


- A diagnosis of MM as defined as any patient with detectable M-protein in blood and/or
urine, monoclonal plasma cells in the bone marrow, and evidence of end-organ damage (based
on the International Myeloma Working Group's diagnostic CRAB criteria:

hypercalcemia [serum calcium at least 1 mg/dL above the upper limit of normal], renal
failure [creatinine greater than 1.95 mg/dL), anemia (hemoglobin less than 10 g/dL], or
bone lesions [lytic lesions or osteoporosis with compression fractures]).

- Patients who have received previous therapy for MM.

Type of Study:


Study Design:

Time Perspective: Prospective

Principal Investigator

Carl O Landgren, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

April 2010

Completion Date:

Related Keywords:

  • Smoldering Myeloma
  • Monoclonal Gammopathy of Undetermined Significance
  • Plasma Cell Neoplasm
  • Natural History
  • Translational Studies
  • Gene Expression Profiling
  • Protein Markers
  • Smoldering Myeloma
  • SMM
  • Monoclonal Gammopathy of Undetermined Significance
  • MGUS
  • Monoclonal Gammopathy of Undetermined Significance
  • Paraproteinemias
  • Multiple Myeloma
  • Neoplasms, Plasma Cell



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892