The current standard for staging multiple myeloma is now the International Staging System (ISS), according to Leukemia magazine.

The main focus of the ISS is a readily available laboratory test called the serum beta-2 microglobulin test. Beta-2 microglobulin is plentiful on the surface of white blood cells. Increased production or destruction of these cells causes beta-2 microglobulin levels in the blood to increase. This increase is seen in people with cancers involving white blood cells, but it is particularly meaningful in people newly diagnosed with multiple myeloma. Measurements obtained from the beta-2 microglobulin test and albumin levels in serum are used to categorize patients as stage I, stage II, or stage III. Each stage is given a median survival time. Stage I has a median survival time of 62 months, stage II is 44 months, and stage III is 29 months.

One major benefit of this system is that results can be easily compared, as results come from laboratory tests and not subjective observations. Additionally, the ISS is more reproducible than the previous staging system.

Limitations currently exist within the ISS system, however. For example, it can only be used once a patient has been diagnosed with multiple myeloma. It also cannot be used to stage any other plasma cell disorders, nor can it distinguish myeloma from them. Another shortcoming occurs in patients who are stage III. ISS may show stage III patients to have an extremely elevated beta-2 microglobulin level due to tumor burden, but the elevated level could instead be caused by kidney failure. Therefore, it is hard to get an accurate tumor burden calculation. Finally, it is unknown how long the ISS staging system will remain relevant as new treatment drugs emerge.

Prior to the ISS, doctors typically used the Durie-Salmon Staging System. Though complicated, the basic premise behind this system is that finding the immunoglobulin production of each plasma cell and the half-life of circulating immunoglobulin allows one to calculate the tumor burden, or the total number of myeloma cells.

The Durie-Salmon Staging System used both tumor burden and individual clinical features, such as hemoglobin levels and number of bone lesions, to stage myeloma. Patients were categorized as either stage I, II, or III, depending on the severity of their anemia, hypercalcemia, and bone lesions, as well as the level of M protein in their serum and urine.

There was a major shortcoming in this staging system, however. One of the staging criteria, the presence of bone lesions, was subjective in nature, based solely on the opinion of the professional observing the patient’s radiograph. A more objective system, the ISS, was thus adopted.

The authors of the Leukemia article recommend that both the Durie-Salmon and ISS staging systems be used to stage myeloma. Though the Durie-Salmon system has its shortcomings, it provides a more accurate picture of tumor burden than the ISS system.

For more information on myeloma staging, visit the full article in Leukemia ^[1]. Also see the previous Beacon article in this series on diagnostic criteria. ^[2] Future installments detailing new information on risk stratification and response criteria in multiple myeloma will follow in the coming weeks.