How Do BCMA-Targeting Bispecific Antibodies Work?

BCMA is targeted by 3 bispecific antibodies in treatment of patients with multiple myeloma due to BCMA’s role in helping cancer cells mature and multiply, explained Caleb Raine, PA-C.

In an interview with Raine after moderating a Case-Based Roundtable hosted by Oncology Nursing News, Raine described how BCMA initiate a process which result in the maturation of plasma cells. When this process occurs in malignant cells, it can cause those cells to multiply, or “inviting people to the party” as Raine described it.

To reduce the ability for cancerous cells to multiply, BCMA-targeted bispecific bodies including teclistamab (Tecvayli), linvoseltamab (Lynozyfic), and elranatamab (Elrexfio) have been approved for use in multiple myeloma.

Raine is a physician assistant at Emory Winship Cancer Institute in Atlanta, Georgia.

Transcript

“BCMA” stands for “B-cell maturation antigen.” All plasma cells have these, and they’re responsible for triggering a chain of events within the cell that allow it to live and mature. When we’re talking about the abnormal plasma cells, things don’t work the way they’re supposed to.

It can set off or trigger a chain of events that allows the cell to survive longer than it should. We don’t want cancer cells to do that, because when they do, they want to start dividing and having friends and inviting people to the party. That’s what we try to avoid.

The thing to remember is that BCMA itself is not necessarily a bad thing. It’s found on all plasma cells. What you’ll see is a higher concentration on the cell surface of the malignant cells. When you think of malignancies, you’re going to have a higher population of the malignant cells, just by nature of what they do. You’re going to have higher concentrations overall in the system of BCMA; historically, higher concentrations of BCMA in myeloma have been associated with poor outcomes.

For that reason, BCMA is a target that has been used. Teclistamab was 1 of the first ones used for BCMA specifically. It was approved and went into use back in 2022 on clinical trial.

The difference there is that normal and malignant plasma cells have this GPRC5D protein that is going to be on both but of course, again, it’s going to be in higher concentration on malignant cells. Drugs like talquetamab (Talvey) specifically bind and target that so that it’s not usable for the malignant cells and it doesn’t create that subsequent elongation of a cell that should already be dead. That’s how they work overall.

This transcript has been edited for clarity and conciseness.