First, we have uncovered a new serum marker for multiple myeloma which is a protein called B-cell maturation antigen or BCMA for short. This protein is shed off the myeloma cells into the blood. We have shown that the levels of BCMA predict outcomes for myeloma patients. Lower levels are associated with better survival. In addition, this protein can be used to follow the response of patients to their treatments. As they respond, the levels drop. As the disease worsens, blood levels of BCMA go up. We have recently shown that this shed protein explains the immune deficiency that leads to the high risk of infection that many patients experience. This circulating BCMA blocks the function of the factors that normally keep the immune system functioning. We are working on ways to prevent BCMA from doing this. In addition, we are continuing to study whether BCMA may be an additional way to monitor myeloma patients’ disease. We are also studying other related diseases such as leukemia and lymphoma to determine whether BCMA may be found in the blood of these patients and also contribute to their increased risks of infection.
Second, we have also identified a factor in myeloma patients that both contribute to myeloma growth and their bone problems which commonly occur in these patients. The factor is called tumor necrosis factor-related activating factor 6 or TRAF6 for short. This factor is found both in myeloma tumor cells and osteoclasts which are the cells in the body that cause bone loss. We have been able to construct compounds that block the function of TRAF6. In our laboratory, these compounds produce anti‑myeloma effects and a reduction in the number of osteoclasts. Thus, it is possible that a single drug may be able to both reduce myeloma and at the same time prevent bone problems.
Third, we continue to make significant progress on developing treatments that will only get rid of the myeloma and leave the rest of the patient alone. Work in our laboratory has shown that it is now possible to target the tumor cell with certain compounds. We can then “piggyback” a drug that is toxic to myeloma on the targeting compound. This approach allows us to deliver much more drug to the myeloma and very little to the remainder of the patient. This research has proven very effective with cure of the cancer in the myeloma models that it has been tested in our laboratory. It is a very promising new treatment approach that will hopefully be in the clinic soon.
Fourth, we continue to use our laboratory to test promising treatments that have been tried on patients in our clinic. These studies are proving very useful in the development of brand new treatments for our myeloma patients.