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Studying the Natural Course of Precursor Conditions to Multiple Myeloma

Name of the Trial

Natural History Study of Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Myeloma (SMM) (NCI-10-C-0096). See the protocol summary.

Principal Investigator

Dr. Ola Landgren
Dr. Ola Landgren
Principal Investigator

Dr. Ola Landgren, NCI Center for Cancer Research  

Why This Trial Is Important

Multiple myeloma is a rare type of cancer in which abnormal plasma, or myeloma, cells collect in the bone marrow and other soft tissue. These abnormal cells can form tumors that damage bone directly. They also produce large amounts of antibodies, known as M proteins, that may collect in and impair the function of the bone marrow and other organs of the body, causing problems such as hypercalcemia, anemia, and organ damage. This disease is currently incurable, and most patients succumb within 3 to 4 years of diagnosis.

Multiple myeloma is preceded by one of two precursor conditions called monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. Both of these conditions are characterized by varying levels of M protein in the blood and/or urine and of plasma cells in the bone marrow. They are distinguished from multiple myeloma by the absence of symptoms. MGUS and smoldering myeloma are usually diagnosed via blood or urine tests for unrelated conditions or as part of a routine physical exam.

MGUS is found in about 3 percent of Caucasian Americans over the age of 50 and is even more prevalent in African Americans, but the vast majority of people with MGUS will never develop multiple myeloma. The risk of progressing to symptomatic multiple myeloma is much greater for those diagnosed with smoldering myeloma: about 10 percent per year progress in the first 5 years following diagnosis. Most of what is known about the progression of these precursor conditions comes from retrospective studies, which may not accurately reflect their true nature. To more accurately characterize the risk and clinical course of these conditions, including defining which patients are more likely to progress and why, prospective studies are needed.

In the current study, doctors at NCI will examine people previously diagnosed with MGUS or smoldering myeloma when they enroll in the study, after 6 months, and every 12 months for up to 5 years. At the beginning and at the end of the study, a bone marrow aspiration and biopsy will be done to characterize the molecular status of the bone marrow. The doctors may collect blood and urine samples and conduct various imaging studies, possibly including a skeletal survey of the head, torso, and upper arms and legs. The researchers hope to determine whether any risk factors or molecular markers can be identified that reliably predict which people will progress to full-blown multiple myeloma.

“All patients who develop multiple myeloma go through a precursor phase of asymptomatic disease, so if we can catch the disease at that point, there may be a possibility of curing it,” said Dr. Landgren. “Therefore, it’s very important to identify the molecular profiles of those people who progress from MGUS or smoldering myeloma and those who don’t.

“Study participants will receive a very extensive clinical work up when they first arrive at NIH, more than would normally be done at a community clinic, and they will undergo thorough testing every year thereafter,” Dr. Landgren added. “If a patient progresses during the course of the study, he or she can either go back to their local doctor for treatment or we can offer therapy at the NIH through clinical trials. Additionally, patients with smoldering myeloma may be eligible to participate in both this natural history study and an ongoing clinical trial testing a novel therapy for smoldering myeloma.”

Similarly, Dr. Landgren’s team has developed advanced molecular imaging studies for MGUS and smoldering myeloma patients. “Patients with either MGUS or smoldering myeloma enrolled in the natural history study may be eligible to also participate in an imaging clinical trial designed to rule out evidence of previously undetected early bone disease.”

For More Information

See the lists of entry criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.

  • Posted: September 20, 2011