The International Myeloma Working Group (IMWG) published what is now the standard response criteria for multiple myeloma, says a recent article in the Leukemia journal.

Though many other organizations created their own response criteria in the past, the IMWG recognized the need for one uniform list of criteria to be used in future clinical trials. The other organizations’ criteria have largely been abandoned following the adoption of the IMWG list in 2006.

Response criteria measure tumor response to treatments, providing a solid base upon which researchers can classify individuals and solidly recognize when improvement occurs.

The IMWG response criteria for multiple myeloma include the following subcategories: Complete response, Stringent complete response, Very good partial response, Partial response, Stable disease, and Progressive disease.

Each one of these subcategories comes with its own set of response characteristics that clearly define the level of response patients exhibit during clinical trials.

Response Criteria for Complete Response (CR)

Patients with CR must show that no abnormal monoclonal proteins (also called M-proteins) are present in the blood serum or urine. Additionally, any soft tissue plasmacytomas, which are malignant plasma cell tumors, must disappear. Finally, their bone marrow should consist of less than five percent plasma cells.

Response Criteria for Stringent Complete Response (sCR)

The criteria for sCR are the same seen in CR with two additions. Firstly, patients must have a normal free light chain (FLC) ratio, a laboratory test that measures the activity of monoclonal proteins. Additionally, there must be an absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.

Response Criteria for Very Good Partial Response (VGPR)

VGPR, according to the authors of the study, is a useful subcategory because it “identifies patients with a better outcome who have achieved excellent response but are not yet in CR.” Patients with VGPR have detectable levels of M-proteins in their serum and urine when immunofixation is used, but not electrophoresis. Alternatively, VGPR patients may be defined as those who have had a 90 percent or greater reduction in their serum M-component, and show less than 100 mg of urinary M-component over a period of 24 hours. The VGPR category has gained clinical significance because patients who obtain this subcategory following their first autologous stem cell transplant do not benefit from a second transplant.

Response Criteria for Partial Response (PR)

PR patients show at least a 50 percent reduction of serum M-proteins and show less than 200 mg of urine M-proteins over a 24 hour period. Additional requirements are given for situations in which M-proteins are immeasurable, which involve reductions in FLC levels and bone marrow plasma cells. In all PR patients, a 50 percent or greater reduction in the size of soft tissue plasmacytomas must be demonstrated.

Response Criteria for Progressive Disease (PD)

The PD subcategory reflects that M-protein, FLC, and bone marrow plasma cell percentages are increasing rather than decreasing. More exactly, there must be a twenty-five percent increase from the lowest response value in any of the previously listed items. Additionally, there must be definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of those that already exist. Finally, the development of hypercalcemia, if caused solely by multiple myeloma, is another indicator of this response subcategory.

Response Criteria for Stable Disease (SD)

The final subcategory is SD, which is that it does not meet the criteria for CR, VGPR, PR, or PD.

The authors of the article feel that the IMWG response guidelines clarify, supplement, and overcome the limitations of previous criteria. However, they do note that the absence of a minor response category in the IMWG criteria is somewhat limiting for patients with relapsed refractory myeloma.

For more information on response criteria in multiple myeloma, please visit the full article. Also see previous Beacon installments in this series on diagnostic criteria, staging, and risk stratification.