CAR-T Cells, Bi-Specific Antibodies Find and Destroy Myeloma

An expert explains how two common myeloma treatments – CAR-T cell therapy and bi-specific antibodies – work, and which patients may want to steer clear from these treatment modalities.

As myeloma treatments continue to expand, it can be difficult to understand the different types of therapies and how they work. In a recent interview with CURE®, Dr. Shambavi Richard went back to the basics and explained what patients need to know about the ever-changing world of multiple myeloma.

“Myeloma has been one of the better fields in malignant hematology in that there’s been so much research and so many new drugs that have been coming up and getting approved in the last few years. And now we have several novel therapies in myeloma, too,” said Richard, an assistant professor of Medicine, Hematology and Medical Oncology at Mount Sinai.

Richard said that CAR-T cell therapy and bi-specific antibodies are two advances that are particularly exciting for the field of myeloma.

CURE®: Can you explain what, exactly, CAR-T cell therapy is and how it works?

Richard: CAR-T cell therapy stands for chimeric antigen receptor T cells. These are T lymphocytes, which are a subtype of white cells that we have in our body as a part of our immune system. These T lymphocytes are extracted from the patient and genetically modified in the lab to be able to express receptors or certain proteins on their surface that will target a specific antigen or another protein that’s on the cancer cell. It binds to it then starts numerous signaling processes in the body that eventually are geared toward killing these tumor cells.

What about bi-specific antibodies?

These are now actually off-the-shelf products. These are drugs (like most others); these are lab engineered. (Bi-specific antibodies) have two protein receptors on them: one that binds to an antigen on the tumor cell, just as the way the CAR-T cell therapy does, and the other now binds to a receptor on the T cell, which is part of our immune system again.

When you give the drug to the patient, these antibodies now bind to the tumor cell, brings the T cell to the tumor cell and effectively causes the killing of the tumor cell.

Are there any patients who should not receive CAR-T cell therapy or bi-specific antibodies?

Most patients can get these treatments. If a patient does not have a good support system and they are very frail, have a lot of other medical illnesses that make them sick or are not in very good shape in terms of their cardiac condition or other things, then perhaps CAR-T cell therapy is not the best for that patient.

But other than that, in terms of bi-specific antibodies, for instance, you really give them to 80-plus year-olds. They are able to really tolerate them quite well. We do a few step-up doses to get them to that full dose, so the body has time to slowly start getting used to it. The hospitalizations are very brief with the initial doses, and then after that they really tolerate them very well.

So the majority of patients are able to get any of these. Other patients that I might hesitate to use these right away might be somebody with (central nervous system) disease, for instance… We expect them to have much more toxicities from this. We know that neurologic toxicities (are common for these therapies). So we may want to be more cautious and really understand how they work in these situations better, and I might hesitate to use them at this moment.

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