Year End 2014

The Institute has been involved in very exciting work this year. We have identified new treatments for myeloma, identified new ways to follow the disease and completed research that has led to a better understanding of the biology of myeloma.

First, we have found that a drug named Jakafi, that is used to treat a bone marrow condition in which patients make too many blood cells, is very effective in treating multiple myeloma, and enhances the effectiveness of other drugs used to treat multiple myeloma including Revlimid and steroids. We are hoping that clinical trials will soon start to show that this therapy can be effective to treat patients in my and other practices.

Second, the work with Jakafi has led to the discovery of a new pathway by our laboratory staff through which this drug can help boost the immune response to the patient’s myeloma. Specifically, a kind of white blood cell called a macrophage, which is a ‘scavenger’ cell, can exist in two forms- one that increases tumor growth and one that slows the growth of the myeloma. We have shown that Jakafi markedly reduces the number of macrophages that make the tumor grow while increasing the level of these types of cells that knock out the myeloma. We have also uncovered the specific pathways in the cell that produce this effect.

Third, we have furthered our work on a new protein marker called B-cell maturation antigen (BCMA) that is found in the blood of myeloma patients. This marker correlates with how the patient is doing in that very low levels are associated with patients being in remission whereas high levels are found among patients who are doing poorly. Moreover, the level of BCMA in the blood can be used to track the disease over time just like conventional testing for the M-protein does for most patients. However, there are some patients who do not make the M-protein and now we have shown that we have a new marker, BCMA, to follow them accurately. Importantly, unlike M-protein that turns over very slowly in the blood (over weeks), BCMA turns over rapidly (one or two days) so that this new test will allow a much more rapid assessment of a patient’s disease status than the M-protein does.

Fourth, a hallmark of myeloma is the associated immune deficiency which often leads to infection and a lack of a patient‘s ability to fight off the myeloma effectively. Until now, it was poorly understood what caused this problem for patients with myeloma. We have now discovered that the same protein that we have identified to track myeloma also causes the immune defects to occur. When BCMA is present in the blood, it binds the substances that drive normal immune cell development, and prevents them from acting to drive normal immune functions in these patients. We are now working on ways to prevent this from occurring so that patients can have functional immune systems that allow them to fend off infections and fight their myeloma more effectively.

We are all very excited about the new discoveries that we have made with your help this year at IMBCR.

James Berenson, MD