BCMA-Targeted Drugs Allow for a ‘More Targeted Killing’ of Myeloma Cells

In recent years, BCMA-targeted therapies have changed the landscape of relapsed/refractory myeloma treatment, filling a previously unmet need.

The use of BCMA-targeted therapies has improved the treatment of patients with relapsed/refractory multiple myeloma, and with the development of bi-specific antibodies, the field will continue to change, according to Dr. Adam D. Cohen, an associate professor of Medicine at the Hospital of the University of Pennsylvania in Philadelphia.

BCMA is a protein expressed on the cell surface of myeloma. Drugs that target BCMA attach to the protein and kill the myeloma cells. This type of therapy is currently being used for patients whose disease stops responding to standard upfront treatments, such as proteasome inhibitors and CD-38 antibodies.

“We know that relapse in that relapsed/refractory population and response rates and (progression-free survival, the time from treatment until the disease worsens) and survival is poor,” Cohen said. “It was really an area of unmet need. Fortunately, the BCMA-targeted therapies are trying to fill that niche right now.”

The first BCMA-targeted therapy for pretreated relapsed/refractory myeloma to be approved by the Food and Drug Administration (FDA) was Blenrep (belantamab mafodotin-blmf), which is a drug that is given intravenously once every three weeks and seeks out and kills myeloma cells for a “more targeted killing,” Cohen said.

More recently, the FDA approved two CAR-T cell therapies (another type of BCMA-targeted therapy) for patients with relapsed or refractory myeloma: Carvykti (cilta-cel) and Abecma (idecabtagene vicleucel).

“These require patients to have T cells collected from the blood to actually sit on a machine called a pheresis machine. Some T cells are taken out of the blood. Those cells are then shipped off to a manufacturing company where they modify those T cells to now be able to recognize and kill the cancer cells, the myeloma cell in particular…. They then ship it back to the treating hospital where they're then infused into the patient,” Cohen explained, noting that while the process can take up to four to six weeks and require hospitalization, one CAR-T cell therapy treatment could allow patients to go months — or even years — without needing treatment again.

Side Effects from BCMA-Targeted Therapies

Like other cancer drugs, Blenrep use is associated with side effects, namely damage to the cornea, which is the protective layer of the eye, which can result in dry eye or blurry vision.

However, with the collaboration of an oncology team and an optometrist or ophthalmologist, to properly adjust the drug dosage, the side effect can be reversed.

“So that’s the one thing with (Blenrep) to keep an eye on, no pun intended,” Cohen said.

For the CAR-T cell therapies, patients and their providers should look out for neurotoxicity and/or cytokine release syndrome, which is when the body releases too many inflammatory molecules called cytokines.

“We’ve learned how to really manage these with aggressive supportive care and, in some cases, (Actemra [tocilizumab]) or steroids to try to minimize the risk of these becoming severe,” Cohen said.

With BCMA-targeted therapies in general, patients can experience hypogammaglobulinemia, which is an issue with the immune system where the body fails to produce enough immunoglobulins, a type of antibody. As a result, they can be at an increased risk for infections for months after treatment.

“These patients often receive (intravenous immune globulin) replacement, and need to be monitored closely with prophylactic anti-microbials as needed, and (receive) prompt treatment at any signs of infection,” he said.

New Therapies Are Being Explored

While these new therapies are exciting, and vastly improving the outcomes of patients with relapsed/refractory multiple myeloma, more improvements are coming down the pipeline, too.

“(The space is) going to continue to change because there are … other types of BCMA-directed therapies that are coming out next,” Cohen said. “They’re called bi-specific T-cell engagers.”

Cohen explained that bi-specific T-cell engagers (known as BiTE therapy) is another approach to “wake up the immune system to attack the myeloma.” These drugs are typically given via infusion or injections under the skin and are similar to CAR-T cell therapies but do not use the patient’s own T cells.

Since BiTE therapy does not include the process of extracting and manufacturing patients’ T cells, the treatment can happen right away, as opposed to the CAR-T cell process, which can take weeks. On the downside, however, BiTE therapy does not have the same “one and done” approach as CAR-T cell therapy, so patients must continue to receive the treatment every two to four weeks.

“So we don’t know which of these approaches is going to end up being the best,” Cohen said. “In the end, I think they’ll both hopefully be available for patients in the next year or so, and the new can pick and choose how we’re going to use them. It’s always nice to have more options.”

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