According to the results of a recent large Swedish study, patients with the myeloma precursor disease monoclonal gammopathy of undetermined significance may have a higher risk of developing infections than the general population.

The researchers found that patients with monoclonal gammopathy of unde­termined significance (MGUS) were more than twice as likely as the general population to develop either a bacterial or viral infection.

However, they found infections did not increase an MGUS patient’s risk of progressing to multiple myeloma.

The researchers commented that these findings may influence the surveillance and treatment of infections in MGUS patients.

“If our findings are true, then perhaps clinicians should have a lower threshold to suspect infections [in MGUS patients] and possibly treat [them] more aggressively compared to other individuals,” said Dr. Sigurdur Kristinsson from the Karolinska University Hospital in Stockholm, Sweden, and lead investigator of the study.

However, he added, “It is important to note that there is no evidence from clinical trials to support the need for early treatment for infections in MGUS patients compared to the general population. Therefore, at this stage, MGUS patients should be treated according to clinical guidelines.”

MGUS is a plasma cell disorder, characterized by an elevated level of monoclonal protein in the blood. Unlike myeloma patients, however, MGUS patients do not experience any disease-related symptoms and typically do not receive treatment unless their condition worsens.

Results of previous studies have shown that MGUS patients are more likely than the general population to develop bacteremia – a condition characterized by the presence of bacteria in the bloodstream – as well as bacterial infections in the abdomen and upper respiratory tract.

“MGUS patients, like myeloma patients, may have lower normal antibody levels that predispose them to infections. They may also have white blood cells that do not work quite as well as in normal patients,” said Dr. James Berenson of Berenson Oncology in West Hollywood, California, who was not involved in the study.

According to the study investigators, however, there has been no comprehensive study assessing the risk of a broad range of bacterial and viral infections in a large population of MGUS patients.

In the current study, researchers analyzed data from 5,326 MGUS patients diagnosed in Sweden between 1965 and 2005, as well as 20,161 healthy individuals. The median age of both the MGUS patients and healthy individuals was 71 years.

The researchers found an average of 0.34 infections per MGUS patient, compared to 0.17 infections per healthy individual. In addition, 7.1 percent of MGUS patients developed more than one infection, compared to 2.7 percent of healthy individuals.

Compared to the healthy individuals, MGUS patients had a 2.1-fold and 2.2-fold increased risk of developing any form of infection after five and ten years, respectively. This risk was highest for patients with monoclonal protein levels above 2.5 g/dL.

More specifically, MGUS patients had a 2.1-fold and 2.2-fold increased risk of developing a bacterial infection after five and ten years, respectively. After ten years, they had an increased risk of developing bone infection (3.3-fold), meningitis (3.1-fold), blood poisoning (3.1-fold), kidney infection (2.5-fold), pneumonia (2.4-fold), heart inflammation (2.2-fold), and skin infection (1.9-fold).

Dr. Kristinsson explained that the increased rate of bacterial infections observed in the MGUS patients may have been caused either by the MGUS itself or by another underlying disease.

“The major immunological defect in multiple myeloma is in the [blood], with a diminished production of [proteins in the immune system] which leads to a defective antibody response. In MGUS, [antibody protein deficiency] occurs in 25 percent to 28 percent of all cases,” said Dr. Kristinsson.

However, he acknowledged, “It is possible that many MGUS patients have another underlying disease that may be associated with an increased risk of bacterial infections, such as autoimmune diseases.”

MGUS patients also had a 2.7-fold risk of developing a viral infection after both five and ten years. After ten years, they had an increased risk of developing shingles (2.8-fold) and the flu (2.7-fold).

The researchers pointed out that multiple myeloma patients may have an increased risk of developing viral infections mainly because of therapeutic side effects. For instance, patients treated with Velcade (bortezo­mib) have been shown to have an increased risk of developing herpes zoster.

However, because MGUS patients do not receive any form of treatment, the cause of their increased risk of developing viral infections is unclear to Dr. Kristinsson.

“No other study has observed [why MGUS patients are more likely than the general population to develop viral infections], and we feel that our findings need to be confirmed in other studies,” he explained.

Dr. Berenson, however, suggested that MGUS patients are more likely to develop a viral infection compared to the general population because of defects in the virus-fighting components of their immune system.

“[MGUS patients] may be predisposed to viral infections because they have a defect in the part of the immune system that helps fight off viruses,” said Dr. Berenson.

“It is known that myeloma patients often have a defect in T lymphocyte function, which may be true in MGUS as well. These types of white blood cells help prevent viral infections,” he added.

Although previous studies have shown that a history of infections increases the risk of developing multiple myeloma, the researchers found that MGUS patients who developed an infection were as equally likely to progress to multiple myeloma as MGUS patients who did not develop an infection.

“I think that an infection in MGUS patients does not predispose them to myeloma,” said Dr. Berenson.

For more information, please see the study in the journal Haematologica (pdf).