Research Update July 2018

Dear Friend:

We wanted to give you an update on the extremely important and successful work that the Institute for Myeloma & Bone Cancer Research (IMBCR) has undertaken during the past six months as we continue our groundbreaking research into finding a cure for multiple myeloma and other bone cancers.

IMBCR remains the only independent non-profit cancer research institute working to find improved treatment, and ultimately a cure, for multiple myeloma, a cancer of blood cells that reside in the bone marrow. While the focus of the research is multiple myeloma, many therapies discovered in our research laboratory can apply to the treatment of other cancers, particularly cancers that spread to the bone such as prostate, breast and lung cancer.

Because of our research, we have continued to develop new treatment regimens that have benefited patients with multiple myeloma and other blood cancers. To continue our research, we need additional funds and we now ask for your financial support.

IMBCR continues to be involved in very exciting work. We have identified new treatments for myeloma, identified innovative ways to follow the disease, and completed research that has led to a better understanding of the biology of myeloma.

First, we have continued our protein marker called B-cell maturation antigen (BCMA), which is found in the blood (serum) of myeloma patients. With this simple blood test, we can predict a patient’s likelihood to respond to specific treatments and their long-term outcome with the disease. It also provides a much more rapid way to determine whether a patient is responding to their treatment than currently available tests, which will allow doctors to make much quicker changes to a patient’s treatment- in days instead of months. For myeloma patients whose serum and urine does not have the conventional blood markers, we have shown that serum BCMA levels can be used to monitor them rather than the invasive bone marrow exams and PET scans that are required to follow their disease presently.

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 the course of their disease.

Third, we have also established that serum BCMA levels are extremely low in patients with immune deficiencies and associated with disease-related complications in these patients. This likely represents the first blood test to both diagnose and predict clinical problems in patients with primary immune deficiencies.

Fourth, we have now shown that low levels of BCMA predict poor outcomes for patients with breast cancer and expect that this is likely to be the case in many other types of cancer that we are now testing.

Fifth, 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. We have now discovered that this same protein, BCMA, when present at high serum levels in myeloma patients, causes the occurrence of their immune defects. We are now working on ways to prevent this from occurring so that myeloma patients can have functional immune systems which will allow them to fend off infections and fight their myeloma more effectively.

Sixth, we have shown that serum levels of BCMA interfere with the targeting of BCMA on tumor cells by new immune-based therapies. Our results with an inhibitor of the enzyme, gamma secretase, that leads to the shedding of BCMA show that we can prevent it from being released off the myeloma cells. This is likely to pave the way for a multitude of studies to use this approach to reverse this “blocking” effect of serum BCMA which should improve the effectiveness of BCMA targeted approaches and reverse the immune deficiency that results from serum BCMA sequestering the proteins that allow the immune system to function properly. The use of these inhibitors is now being used as part of the treatment for patients receiving agents targeting BCMA.

Seventh, we are also carrying out further work on a drug called Jakafi (ruxolitinib). We have shown that this drug increases the effectiveness of a variety of other drugs that are currently used to treat myeloma including the combination of Revlimid and steroids. A clinical trial was conducted with this combination for myeloma patients. It has shown that patients doing poorly on Revlimid and steroids respond with the addition of Jakafi, and the regimen has been very well tolerated. The results of this study were recently presented at the annual meeting of the American Society of Clinical Oncology meeting in Chicago. More trials are planned to expand the use of this highly effective and well tolerated treatment for myeloma patients. We have shown a newer version of Jakafi is in early development and we have shown that this new drug has major activity against myeloma, especially when combined with other anti-myeloma drugs.

Eighth, 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 which increases tumor growth and the other which 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 types of these cells that eliminate the myeloma. We have also uncovered the specific pathways in the macrophage that produce this effect. Recently, we have shown that Jakafi markedly specifically reduces a protein that is responsible for resistance to Revlimid which helps explain the specific ability of Jakafi to overcome resistance to Revlimid in myeloma patients. We have also uncovered a new mechanism through which Jakafi works- reducing the levels of proteins called PD-L1 and PD-L2 that are on the tumor cell and block immune responses to the myeloma.

Ninth, 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 have now identified specific ones associated with sensitivity and resistance to several anti-myeloma drugs which will help make more effective treatment planning decisions for individual patients.

Tenth, we have been working on a new, exciting approach to treat myeloma that will only eliminate the tumor cells without having any side effects. This is a treatment that will target the genetic material that is only present in the tumor cells allowing tumor specific killing without any side effects.

We are all very excited about the new discoveries that we have made to make the lives of patients with myeloma better. The advancements during this year at IMBCR would not have happened without your generous support.

We count on our many donors and financial supporters to continue with their remarkable efforts in funding our research and we have enclosed both a Pledge Card and a reply envelope for your use.

If it is more convenient, you can make a secure online credit card donation by visiting our website: www.imbcr.org. Please click on the “Donate Now” button.

You can also make a credit card donation by telephoning our main office number: (310) 623-1210.

In advance, we thank you for your donation and, if you have any questions or comments, please do not hesitate to contact either of us at the above telephone number.

With thanks and best wishes.

James R. Berenson, M.D. Geoffrey M. Gee, Esq.
President, Medical and Scientific Director Executive Director