First, we have made much progress on our new protein marker called B-cell maturation antigen (BCMA) that was initially found in the blood of myeloma patients. The level of this single serum marker predicts patient’s long-term outcomes. It also correlates with how the patient is doing in that very low levels are associated with patients doing well on their therapy 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. Importantly, unlike M-protein that turns over very slowly in the blood (over weeks), BCMA turns over rapidly (one or two days). Because of this, we have now shown that we can determine a patient’s response to their treatment within the first week of new therapy rather than have to wait for a month as is the standard of practice with currently available blood and urine tests. This will allow doctors to make much quicker decisions about the effectiveness of a treatment allowing changes to be made in the patient’s treatment if it is not working both sparing the patients of experiencing potential side effects and shortening the time that the patient has to stay on an ineffective regimen. In addition, there are some patients who do not make the M-protein and we have shown that their disease can be tracked with this new marker.
Second, we have now established that serum BCMA can be used to track and predict outcomes for patients with other related cancers including Waldenstrom’s macroglobulinemia and chronic lymphocytic leukemia. Patients with the latter disease do not currently have any serum marker to chart their course of disease. We are also testing whether serum BCMA will also be able to be used for following patients with lymphoma, a disease also lacking any serum markers to follow it.
Third, 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, BCMA that we have identified to track myeloma also causes the immune defects to occur in these patients. 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.
Fourth, we have furthered our work on a drug named Jakafi. It is currently used to treat a bone marrow condition in which patients make too many blood cells. We have shown that this drug increases the effectiveness of a variety of other drugs that are currently used to treat myeloma including Revlimid and steroids. As a result of our promising preclinical work, clinical trials will start with this combination in the next several months. Moreover, a newer version of Jakafi is in early development and we are currently evaluating this agent in our laboratory both alone and in combination with other anti-myeloma drugs. These studies will lead to clinical trials to evaluate the most promising combinations in the next few months.
Fifth, we have furthered our work on the pathway that we recently uncovered through which Jakafi 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 eliminate the myeloma. We have also uncovered the specific pathways in the macrophage that produce this effect.
Sixth, we are also working on specific genetic signatures that identify resistance and sensitivity to a variety of currently used drugs for treating myeloma patients. We hope to identify specific signatures that will allow us to better personalize the most effective treatments for our myeloma patients.
We are all very excited about the new discoveries that we have made with your help this year at IMBCR.
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