Myeloma Precursor May Cause Disease Progression, Even 30 Years Later

An abnormal protein found in the blood — called monoclonal gammopathy of undetermined significance (MGUS) – may lead to multiple myeloma progression, even after 30 years of disease stability, according to study results published in the New England Journal of Medicine.

MGUS is a condition where an abnormal protein, known as monoclonal protein, is found in the blood. This condition usually does not cause any problems; however, multiple may develop over time in patients who have it.

“MGUS is present in more than 3 percent of the general population aged 50 and older,” lead author S. Vincent Rajkumar, M.D., a hematologist at Mayo Clinic, said in a press release. “In some cases, people with MGUS go on to develop multiple myeloma.”

Rajkumar and colleagues from the divisions of hematology, biostatistics and epidemiology at Mayo Clinic identified 1,384 patients whose MGUS was diagnosed at the institution from 1960 through 1994. Their aim was to determine whether MGUS led to progression to multiple myeloma or another plasma-cell or lymphoid disorder.

Patients were followed for approximately 34.1 years. In that time, MGUS progressed in 147 patients (11 percent) — a rate that was 6.5 times as high as the rate found in the control population.

The overall risk of progression to myeloma or a related disorder was relatively small at 1 percent each year; however, the risk persisted indefinitely. Without accounting for death due to competing causes, the risk for multiple myeloma 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.

The researchers noted that the risk of myeloma or other related cancer appeared relatively small compared to other general causes of death. As a result, they recommended for patients to be checked for the presence or absence of progression, and to also receive all other routine preventive services appropriate for them as they age.

Adverse risk factors also made these odds worse for patients with immunoglobulin MGUS. The presence of two adverse factors — an abnormal serum free light-chain ratio and a high serum monoclonal protein – was associated with a 55 percent risk at 20 years compared with patients who only demonstrated one of the risk factors (41 percent) and those with neither risk factor (19 percent).

Similarly, among patients with non-immunoglobulin MGUS, risk for progression was 30 percent at 20 years for those with two risk factors, 20 percent in those with one, and 7 percent in those with neither.

Patients with MGUS also had shorter survival (8.4 vs. 12.4 years) compared with the control population that was matched for age and sex.

“We also found that patients with MGUS had shorter survival than comparable people without the condition,” Rajkumar said. “Which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study.”