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The immune system normally helps your body fight off infections, and it also detects and destroys abnormal cells. Antibodies are a key part of the immune system, and these Y-shaped proteins normally help the body recognize pathogens such as viruses and bacteria. Antibodies bind to unique molecules on the outside of cells known as antigens (ie, CD20 is an antigen expressed on the surface of B cells).
Monoclonal antibodies (ie, rituximab) are already widely used in the treatment of chronic lymphocytic leukemia (CLL). These are lab-created antibodies are designed to mark cancer cells by binding to specific targets such as CD20, and they help the immune system better recognize and destroy cancer cells. Now there is a new class of immunotherapy drugs known as bispecific antibodies, which are being studied for the treatment of lymphomas and leukemias.
At the annual meeting of the American Society of Hematology (ASH) 2020, our own Dr. Brian Koffman interviewed Dr. Lindsey Roeker, a hematologic oncologist at Memorial Sloan Kettering Cancer Center. They discussed epcoritamab, a new bispecific antibody, that is currently being tested in clinical trials.
- A bispecific antibody or bispecific T-cell engager (BiTE) brings your immune cells in close proximity to cancer cells.
- Epcoritamab uses one arm of the Y to bind CD3, which is on the surface of T cells, and the other arm to bind CD20, which is on the surface of CLL cells. This brings the T cell and CLL cells close together so that the T cells can better recognize and destroy the CLL cells.
- This is not unlike what happens with CAR-T cells that have been genetically re-engineered to recognize a cancer cell.
- The side effect profile of bispecific antibodies has generally been similar to that of CAR-T therapy. Because T cells are being activated by these treatments, patients can experience cytokine release syndrome.
- Because of the use of CAR-T therapy, we are now pretty experienced at managing cytokine release syndrome. Symptoms of cytokine release syndrome include fever, shaking, and chills.
- Neurotoxicity has been a rare side effect thus far in clinical trials, but it is something that researchers monitor for.
- Bispecific antibodies are an “off-the-shelf” therapy, meaning that you don’t have to wait weeks for it to be manufactured as you do with CAR-T therapy. This can be important in aggressive disease. It also means because they are not specific to each recipient, cost savings may be realized.
- Currently, epcoritamab is being tested in a phase 1B trial that is open now in 16 different sites. Safety has already been established in other lymphomas, and now they are testing it in CLL.
- Researchers are studying two different dose levels of epcoritamab in patients who have already received at least two prior therapies for CLL, including at least one BTK inhibitor.
We know that BTK inhibitors and venetoclax work well for treating CLL, so those are usually our first two treatment options. However, what to use after those drugs is a bit more of an open question. Bispecific antibodies will likely have a place in CLL treatment in the future depending on how well they work.
If you are interested in participating in a clinical trial of epcoritamab, more information can be found at the following website:
Please enjoy this brief interview with Dr. Roeker from the virtual ASH meeting which was held in December 2020. She does a great job explaining this new technology being studied on CLL.
Take care of yourself first.
Ann Liu, PhD