Exciting, new approaches to myeloma treatment
are now being developed and tested in the clinic

We have made continued progress both in our discovery of new treatments for myeloma and ways to monitor the disease. Our work in the research laboratory has uncovered a new approach to myeloma that is now being tested in the clinic. The laboratory findings show that this new approach results from the effects of these drugs on not only the myeloma tumor cells but other types of cells that help the tumor grow. These other cells are a type of white blood cell called a monocyte which can exist in forms that either causes the myeloma to grow or go away. Like a switch, the drugs we are studying are the types that make the tumor grow go away. We have also shown that these drugs allow other drugs that are used to treat myeloma to work better. This is now being translated into clinical trials that have now started!

Our work on B-cell maturation antigen (BCMA) continues to move quickly ahead. It turns out many companies are targeting this same protein to treat myeloma with early promising results through immune-based approaches including antibodies alone or combined with toxic chemicals or T-cells. Our new serum BCMA assay is now being used to predict who might respond to these types of approaches. Compared with conventional blood tests to follow myeloma patients, serum BCMA is able to track a much higher percentage of myeloma patients undergoing new treatments. We have also continued to show that this new marker allows one to determine much more quickly and accurately whether a new treatment is working–within days instead of months! It also appears to help optimize scheduling of drugs. Since it changes so rapidly during treatment, short breaks in therapy with some of the drugs appear to allow the disease to get worse. Assessment of serum BCMA may in the future lead to use of fewer drugs and at lower doses since one may be able to determine quickly whether these better tolerated therapeutic approaches are working allowing many patients to avoid the unnecessary use of more aggressive and costly combination regimens. The current tests including bone marrow sampling that are used to predict outcomes for myeloma patients are both costly and invasive. In contrast, we have now shown that measurement of serum BCMA predicts outcomes for myeloma patients with a simple blood test. We are now collaborating with many groups to measure serum BCMA on their patients with myeloma and other related diseases.

We are also trying to prevent shedding of BCMA from the surface of myeloma cells. Our early results that block the action of the protein, gamma secretase, responsible for the shedding of BCMA are very promising. We hope to accomplish several important things with this new approach. First, we have previously shown that the BCMA that is shed into the blood causes the immune deficiency that is a hallmark of myeloma. Preventing the shedding should reverse the immune deficient state that these patients experience. Second, treatments directed at BCMA which are now being tried much more often as outlined above may be more effective if shedding is prevented. There will be more BCMA on the myeloma cell instead of in the blood for the treatment to target. Moreover, the BCMA in the blood may prevent the treatment from reaching the BCMA–expressing myeloma tumor cells in the bone marrow so that reducing its blood levels should overcome this problem with any type of therapy targeting this protein for myeloma.

It is a very exciting time at IMBCR with lots of very promising new findings from our research!

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