Your questions about BCMA and multiple myeloma, answered
You may have heard someone with multiple myeloma mention the possibility of BCMA-targeted therapy and wondered what BCMA means and why it is relevant in cancer treatments.
For answers to these questions and more, we spoke to Hans Lee, M.D., director of multiple myeloma clinical research at MD Anderson.
What is BCMA?
BCMA stands for B cell maturation antigen, and it's emerged as an important target in multiple myeloma over the last five years or so. Even though myeloma is the second-most common blood cancer, it is considered a rare cancer — much rarer than solid tumors cancers such as colorectal cancer, breast cancer or lung cancer. And although there are fewer patients with this type of cancer, there have been several new drugs developed for multiple myeloma in recent years that have significantly improved patient outcomes.
What is BCMA a marker for?
BCMA is highly expressed — or highly shown — on the surface of myeloma cells. That makes it also a very attractive drug target, so there have been several clinical trials looking at drugs that target BCMA.
What drugs or therapies target BCMA?
There are a few drugs and therapies that target BCMA. The first is chimeric antigen receptor (CAR) T cell therapy, and there are now two FDA-approved BCMA CAR T therapies (idecabtagene vicleucel and ciltacabtagene autoleucel) available. BCMA CAR T therapies have shown strong efficacy, and it is very nice for patients to potentially be off all treatment after receiving a single CAR T infusion. However, access to myeloma CAR T remains limited, and the time it takes for CAR T to be manufactured and ready to give to a patient reduces their role in patients in immediate need of treatment.
The second is bispecific BCMA-directed CD3 T cell engager, which is a more conventional drug. These drugs, also called BCMA bispecifics, are “off the shelf.” This means that there's no need to wait for the therapy; patients can get their treatment when they need it, right away. And so, the Food and Drug Administration (FDA) approved the first BCMA bispecific, teclistamab, in October 2022. There are several clinical trials for similar drugs across the United States and others in development, and all have shown unprecedented efficacy in relapsed and refractory multiple myeloma for an off-the-shelf product.
I use both for my patients, depending on their individual circumstances, and both are going to be very important for multiple myeloma therapy. Because bispecifics for myeloma are relatively new and require hospitalization for the first several doses to monitor for side effects, they are generally only available at more specialized cancer hospitals like MD Anderson. Hopefully, that will change in the future, and more myeloma patients will have access to bispecific drugs in the community as the familiarity and logistics of administration improve.
What sort of patients are offered BCMA therapy?
Patients with relapsed refractory multiple myeloma are good candidates for BCMA therapy. Currently, BCMA-targeted therapies with CAR T and bispecifics are approved for patients with at least four prior treatment regimens that have included the three main classes of myeloma therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.
Historically, new drugs have had response rates of about 30% in patients with relapsed refractory multiple myeloma. This means about 30% of patients have some reduction in their myeloma levels. On the other hand, for the new BCMA drugs with bispecifics and CAR T, the response rates range from 60% to 90%.
Why is BCMA a good drug target?
BCMA has biological significance: it's important for B cell signaling and plasma cell persistence and growth, so it's typically expressed on the B cells and plasma cells.
We're always concerned about the on-target or off-target effects of different treatments, and so far, BCMA seems to be a fairly clean target. These drugs primarily target myeloma cells or plasma cells and leave other cells alone, which makes them attractive.
What would you like patients to know about BCMA bispecifics?
BCMA bispecifics are a fairly new type of myeloma therapy, and we’re offering them here at MD Anderson, along with clinical trials of new treatment options.
There are a lot of trials looking at bispecific antibodies in different contexts, including in different antigens or different targets, other than BCMA. They have shown a lot of promise in clinical trials, and we have several here at MD Anderson in our myeloma group that are ongoing or planned. There are also trials looking at using bispecific antibodies in earlier lines of therapy, where the patients aren’t required to have tried four other treatment regimens before being prescribed one.
This is just the beginning of immunotherapy in myeloma, and it will be a very important modality for treating patients moving forward. I tell my patients that even five years from now, treatments will be ahead of where they are today, and we are far ahead of where we were even a few years ago. I think that there have been very, very tangible improvements, not only for the survival of people with multiple myeloma but for their quality of life as well.