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Paradigm Shift: MGUS, Smoldering Myeloma, And Multiple Myeloma Are All One Disease

11/13/2010 0 Comments Contact Our News Editors

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By Carole S. Giampalmi

Until 2009, it was generally accepted that monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma, and multiple myeloma were three distinctly separate diseases.

If MGUS was accidentally discovered during a patient’s routine medical testing, the patient was often advised to ignore the abnormal test results for the foreseeable future. Most clinical settings encouraged only infrequent routine monitoring, since both MGUS and smoldering myeloma conditions were considered distinct diseases with a small probability of the patient developing multiple myeloma. Often the patient’s personal primary care physician provided any follow-up periodic monitoring.

2009 Study Finds MGUS Phase Present In All Multiple Myeloma Patients
In May 2009, a just completed prospective study, “Monoclonal Gammopathy of Undetermined Significance (MGUS) Consistently Precedes Multiple Myeloma,” published in the prestigious journal, Blood, changed the myeloma landscape forever, and for the better for all pre-myeloma patients. A group of researchers including lead researcher Dr. Ola Landgren of the National Institutes of Health determined that MGUS consistently precedes multiple myeloma.

These three conditions are not separate diseases but one disease on a continuum; all multiple myeloma cases are preceded by an MGUS/smoldering myeloma phase, whether it is identified or not.

[MGUS is clinically defined as having less than 10 percent plasma cells in the bone marrow and less than 30 g/l monoclonal protein (M-spike) in the serum; smoldering multiple myeloma has greater than 10 percent plasma cells in the bone marrow and greater than 30g/l M-spike in the serum; multiple myeloma adds CRAB (increased Calcium, Renal function abnormalities, Anemia, and Bone involvement) findings to the increased plasma cell and M-spike numbers.]
This study discovered that, “Multiple myeloma is universally preceded by a prolonged premalignant stage with up to 75 percent of multiple myeloma patients having detectable M-protein eight or more years prior to diagnosis of the malignancy.” The study’s authors further discovered that the, “well-documented 1 percent annual average risk of multiple myeloma progression among MGUS patients is highly heterogeneous and emphasize the fact that the risk of developing multiple myeloma varies greatly among patients diagnosed with MGUS.”

This landmark study recommended further research to examine the molecular pathways of disease leading from MGUS to smoldering myeloma to multiple myeloma. With these proposed additional studies, it is hypothesized that myelomagenesis pathways will be identified, which would then make possible the identification of steps, or development of compounds, to prevent or delay progression of one of these two earlier phases.
New 2010 Study To Identify Risk Factors Leading To Multiple Myeloma
Just one year later, the National Institutes of Health (NIH) has initiated a recommended follow up study, “Natural History Study of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM).” This study is designed to follow either MGUS or smoldering myeloma patients for up to five years or to the time of progression to multiple myeloma if that occurs during the study period. The objective of the study is to identify risk factors that may cause MGUS and smoldering myeloma to progress to multiple myeloma.
There are currently 26 patients enrolled with an additional 14 anticipated by October. The full study cohort will be 356 people, comprised of 256 MGUS patients and 100 smoldering multiple myeloma patients. Patients enroll at the NIH in Bethesda, Maryland, a northwest suburb of Washington, D.C., easily reached by thousands of individuals.

The first day of the initial visit to enroll in the study includes routine blood and urine tests, a skeletal survey series of x-rays, and a meeting with the research staff for an intake interview to collect medical history data. The second day includes a bone marrow biopsy performed by an expert physician’s assistant. These tests are necessary to confirm either an MGUS or smoldering myeloma state in order that the study’s conclusions will be deemed valid by the scientific community.
During a second one-day trip to the NIH six months later, only blood and urine will be collected. After that second six month visit, a study participant returns annually for up to five years total depending on whether there is progression. At either of those endpoints, five years or progression, the second and final bone marrow biopsy is performed.
NIH Study Results Are Critical To Future Disease Prevention Strategies

This newest study is the logical progression to the earlier 2009 study mentioned in this article. It is a critically important study for all MGUS or smoldering myeloma patients because it is the first attempt to identify the molecular pathways from an earlier phase of disease to multiple myeloma. Only armed with that information can we hope to develop steps to prevent or delay progression in appropriate patients such as high-risk MGUS or smoldering myeloma.
I urge any MGUS or smoldering multiple myeloma patient who can travel to the NIH to enroll in this study as soon as possible. Our individual participation in studies and trials is the key to finally conquering myeloma. Each precious year brings us closer to that goal.
Please contact the research nurse, Mary Ann Yancey, at 301-435-9227 or yanceym@mail.nih.gov for additional study information or to discuss enrolling. You may contact me directly at thecookandbaker@comcast.net for additional information about my personal experience at the NIH.
Carole S. Giampalmi is a smoldering myeloma patient who entered the NIH study in July.

News Source: 
Myeloma Beacon
Rare Disease of Interest: 
Multiple Myeloma