In a recent multi-center study, Spanish researchers identified several immune system characteristics of multiple myeloma patients who have achieved long-term disease control.

They found that patients who achieve long-term disease control have a distinct immune system profile that differs from patients with active disease and from that of healthy adults.

This distinct profile, the researchers argue, likely plays a role in the patients achieving long-term control of their myeloma, and thus deserves further investigation.

The majority of multiple myeloma patients relapse within a median of three years from their initial diagnosis. However, according to the study investigators, 6 percent to 18 percent of treated patients experience 10 or more years without relapse. Notably, this subset of patients includes both those who achieve a complete response and those who revert to a status similar to monoclonal gammopathy of undetermined significance (MGUS), a precursor to myeloma.

Previous evidence has shown that the immune system is impaired in patients with active multiple myeloma. Components of the immune system -- including T cells, B cells, natural killer cells, and dendritic cells -- are considerably altered.

T cells, B cells, and natural killer cells are types of white blood cells, which help the body defend itself against infections and foreign materials.  Natural killer cells, in particular, respond quickly to tumor formation.

Dendritic cells help T cells and B cells identify and attack threats to the body, and they also aid in the development of mature B cells.

In patients with active myeloma, both CD8+ T cells and natural killer cells have been found in increased numbers in both the bone marrow and the circulating blood. CD8+ T cells are a type of T cell that targets cancer cells.

Additionally, B cell precursors and normal plasma cells have been shown to decrease in number in newly diagnosed myeloma patients. Many B cells develop into plasma cells, which produce antibodies needed to fight off infections.

Prior studies also have reported a reduction in dendritic cells in patients with multiple myeloma.

In the current study, researchers sought to investigate the role of these immune cells in patients with long-term disease control. They evaluated data from 28 patients with long-term disease control, 23 patients with newly diagnosed MGUS, 23 patients with active multiple myeloma, and 10 healthy adults of a similar age.

Patients categorized under long-term disease control had either achieved a complete response and remained relapse-free for more than five years or had achieved a partial response to a near complete response and remained relapse-free for three or more years without therapy.

Similar to patients with MGUS and active multiple myeloma, patients exhibiting long-term disease control showed increased levels of CD8+ T cells and natural killer cells. The study investigators concluded that this increase may reveal a mechanism by which tumor growth is controlled.

Patients with long-term disease control were also found to have a reduction in bone marrow regulatory T cells compared to patients with active multiple myeloma.

Regulatory T cells suppress the immune system, and prior studies have produced conflicting results concerning the change in regulatory T cell numbers in myeloma patients. The investigators of the current study hypothesized that the reduction of regulatory T cells in patients with long-term disease control may allow CD8+ T cells and natural killer cells to be more effective in targeting cancerous cells.

Additionally, patients with long-term disease control demonstrated normal B cell levels in both the bone marrow and the circulating blood, while patients with MGUS and active myeloma were depleted of B cells. Consistent with these findings, patients with long-term disease control had increased levels of B cell precursors and plasma cells.

Compared to healthy adults, patients with long-term disease control had similar levels of peripheral blood dendritic cells. These findings are similar to those reported in myeloma patients who remained in remission six months after an autologous stem cell transplant.

The study investigators further analyzed the difference in immune profiles between patients who remained in remission for 10 or more years, those who remained in remission for five to 10 years, and healthy adults.

They found that the patients who experienced 10 or more years of remission had significantly increased numbers of CD8+ T cells, B cells, and particular types of dendritic cells compared to both those who spent less time in remission and healthy adults. Thus, the subset of patients exhibiting long-term disease control do not revert to the immune profile of healthy adults, but rather have their own immune characteristics.

Overall, the authors of the current paper believe their findings indicate that myeloma patients with long-term disease control have improved "immune surveillance," which is the ability of the immune system to identify and eliminate cancerous cells.

This finding, the researchers argue, "deserves further investigation to dissect the specific underlying molecular and functional mechanisms involved."

For more information, please see the study in Haematologica ^[1] (pdf).