At the XII International Myeloma Workshop Saturday, myeloma experts presented their consensus panel report to attendees on the topic of risk stratification in multiple myeloma.

Risk stratification, as defined by the panel leaders, refers to how a patient will progress with myeloma and how to proceed with treatment. The panel’s goal was to propose standard guidelines to evaluate a patient’s risk factors and then determine how to treat such a patient.

For the panel discussion, risk factors did not refer to factors that lead to the development of myeloma, such as age, sex, race, or occupation. Risk factors were rather defined as factors that lead to reduced survival in patients that have been diagnosed with myeloma. These risk factors are normally genetic abnormalities that lead to a higher risk of death, such as the deletion of chromosome 13 in a patient’s DNA.

Because of these genetic variations, the panel proposed evaluating risk factors in clinical trials so that doctors can relate a specific risk factor to the best treatment option. For example, physicians can then determine which novel drugs work well to treat a patient who does not have chromosome 13.

The panel stated that the inclusion of risk factors is important at diagnosis as well as at relapse. Specifically, the panel mentioned that new high risk factors can appear at relapse, and doctors should be able to relate these changes to treatment options.

The consensus is that doctors should look for specific risk factors in patients. The most common evaluation tools fall under the field of cytogenetics, which also includes the technique fluorescent in situ hybridization (FISH).

Cytogenetics looks at specific chromosomal abnormalities in the bone marrow such as chromosome deletions, and FISH looks for the presence of certain chemical “markers” that are present in high risk patients, such as specific DNA sequences.

The panel also discussed the evaluation of these genomic changes. The consensus is that certain chromosomal abnormalities and FISH markers correspond to high risk. Examples would be cytogenetically determined chromosome 13 or 13q deletions or FISH detected DNA sequences associated with chromosomal translocations such as t (4;14) or t (14;16).

A translocation is a rearrangement between two different chromosomes. The translocation t (4;14) means that parts of chromosome 4 and chromosome 14 have broken off and recombined with each other. FISH looks for specific DNA sequences that are present from such translocations. The presence of these factors would lead to higher risk disease.

Unfortunately, the data is not yet available to link these factors to treatment. This heightens the need to include such risk factors in clinical trials.

The panel did not recommend other signs and symptoms as important in determining risk. The consensus is that neither the stage of the disease nor bone information from X-rays or MRI, without cytogenetics and FISH, give clear answers for risk.

The panel was also encouraged by two more recent studies that determined risk by examining the genetics of patients’ myeloma cells. In one trial, they were able to determine the 15 most influential genes that lead to risk. The other trial found 70 genes linked to shorter durations of complete remission, event-free survival, and overall survival.

The goal now will be to link risk factors to therapies. In one case, emerging data is showing that high risk patients, as determined from cytogenetics and FISH tests, have had success with an allotransplant. An allotransplant involves a bone marrow stem cell transplantation between two genetically different individuals. While the report must be confirmed, the panel recommends this treatment option to be considered.

For more information about the meeting, visit the International Myeloma Workshop Web site. A copy of the full risk stratification guidelines can be found here (pdf).