Multiple Myeloma: Better Survival if Precursor State Is Known

Veronica Hackethal, MD

March 12, 2015

Survival is better in multiple myeloma (MM) patients who are aware of their precursor monoclonal gammopathy of uncertain significance (MGUS) than in those who are not, according to a Swedish study published online March 5 in JAMA Oncology.

"Our results reflect the importance of lifelong follow-up for individuals diagnosed as having MGUS, independent of risk score, and highlight the need for better risk models based on the biology of the disease," write lead author Elin Sigurdur Kristinsson, MD, PhD, from the University of Iceland in Reykjavik, and colleagues.

"Patients should receive balanced information, stressing not only the overall very low risk of progression to malignant neoplasm, but also the symptoms that could signal such development and the need to consult their physician," they explain.

Dr Kristinsson and colleagues hypothesized that the prolonged survival in those aware of their precursor MGUS "most likely" reflects more frequent evaluation for progression of MGUS, as well as earlier detection and treatment of MM. Therefore, they ask, could screening be of value?

Although MGUS is common, the general population is not screened for the condition, according to Robert Kyle, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, who is a leader in the field of multiple myeloma and coauthor of an accompanying commentary.

In the white population, MGUS is found in about 3% of people older than 50 years, in 5% of those older than 70 years, and in almost 10% of men 85 to 90 years. In the black population, the percentages are double those of the white population.

Only a modest percentage of cases is picked up during work-up for other issues, Dr Kyle told Medscape Medical News.

However, screening might not be advisable because of the low risk of progression for many patients with MGUS, the potential for patient anxiety related to screening, and the cost of following all the patients identified with screening, he said.

Recent studies have suggested that MGUS consistently precedes the development of MM. Although the risk of progressing from MGUS to MM and related disorders continues throughout life, only a modest percentage of patients do so, Dr Kyle explained.

In fact, over 20 years, only 2% of low-risk patients will progress. The median age of a patient when MGUS is identified is 70 years, so many patients will die of another cause before MGUS progresses.

Once MGUS is identified, the standard is to follow M-protein levels on an annual basis, Dr Kyle said. In practice, though, not all are followed-up.

"It's not feasible to follow all these patients because there are just too many of them," he explained. "What we recommend is that patients with MGUS be followed based on the risk factors for developing multiple myeloma."

The International Myeloma Working Group and the Mayo Clinic recommend a risk-stratified approach that takes into account significant M-protein concentrations (a "spike" greater than 1.5 g/dL), M-protein type (IgA or IgM, as opposed to IgG), and the free light chain ratio, he explained.

"If one takes these three factors — size of the M-protein, type of M-protein, and the free light chain values — one develops a risk-of-progression profile. Patients who fall into the higher-risk groups are the ones who should be followed," Dr Kyle emphasized.

Study Based on Swedish National Registry Data

From national Swedish registries, Dr Kristinsson and colleagues identified all 14,798 patients diagnosed with MM in Sweden from 1976 and 2005 who were followed until 2007.

Median survival was significantly longer in MM patients who knew of their precursor MGUS than in those who did not (2.8 vs 2.1 years; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77 - 0.96; P < .01).

MM patients who knew of their precursor MGUS had more comorbidities than those who did not (P < .001).

For MM patients aware of their MGUS, survival was worse in patients with a concentration of M-protein below 0.5 g/dL at MGUS diagnosis than in those with a concentration above 0.5 g/dL (HR, 1.86; 95% CI, 1.13 - 3.04; P = .01). This could be because patients with low M-protein concentrations were subjected to less frequent follow-up or were lost to follow-up, Dr Kristinsson and colleagues report.

The study authors and Dr Kyle have disclosed no relevant financial relationships.

JAMA Oncol. Published online March 5, 2015. Abstract, Commentary

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