Emerging BCMA-directed CAR T-Cell Therapies in RRMM - Episode 2
Nikhil C. Munshi, MD:I feel the same waythat they are using doublets and triplets or a combination of all of these agents. We have a number of lines of treatment. We now go to later lines—6, 7, and 8 lines of treatment. Transplant still plays a role in the younger patient population, though not so much in the older patient population. But we know that patients eventually relapse. And they eventually, unfortunately, die from myeloma. We still don’t have that proverbial flat curve that says some patients are cured.
So that brings about a need for doing more things, and that’s why you and I keep working in the lab and in the clinic to find new targets, new drugs, and various other options that we can come up with. And so, we now know that one of the good targets is BCMA. What do you think about it? Where the BCMA is located, what it may be doing, signaling wise, etcetera? Where else is it expressed, or why would it be a good target to go after?
Parameswaran Hari, MD, MRCP:Again, you have done a lot of work in this field, obviously. BCMA stands forB-cell maturation antigen, as we know. It is a part of the family of proteins for the TNF [tumor necrosis factor] receptor family. And basically, APRIL [a proliferation-inducing ligand], TACI [transmembrane activator and CAML interactor], and BCMA all interact to provide some signals to myeloma cells and to have long-lived plasma cells. Even in the normal host, you need BCMA signaling. The elimination of BCMA basically leads to depletion of even normal plasma cells.
Nikhil C. Munshi, MD:So I think that’s exactly why it’s been one of our newer targets. And we are utilizing it because the toxicity would be minimal. It’s not expressed on other tissue, normal plasma cells, which you cannot live without. But traditionally, it’s low-functioning cells.
Parameswaran Hari, MD, MRCP:Right, and you can supplement with IVIg [intravenous immunoglobulin] if there’s hypogammaglobulinemia.
Nikhil C. Munshi, MD:Perfect, yes. So I think because of that, we all have great interest, and a lot of other companies have interest in it. And so a number of BCMA-targeting therapies have been utilized, right?
Parameswaran Hari, MD, MRCP:Exactly.
Nikhil C. Munshi, MD:Do you want to tell what those arefrom CAR [chimeric antigen receptor] T cells to other applications of BCMA-targeting agents?
Parameswaran Hari, MD, MRCP:Again, at this meeting and at the International Myeloma Workshop, we saw a number of agents that are coming out. One of the agents that’s probably very close to approval is the antibody-drug conjugate. It had a GSK [GlaxoSmithKline] number, but now we can refer to it by its potential namebelantamab. And this agent, again, is used as a BCMA antibody in conjugation with a toxin called mafodotin, which takes the mafodotin toxin to the surface of the plasma cells.
Then the agents that are in development include chimeric antigen receptor T cells, or CAR T cells, which a plethora of companies are literally working on, and with a variety of viral vectors, or a variety of technologies including CRISPR [clustered regularly interspaced short palindromic repeats]. And then we have agents that are dual bodiesBiTEs [bispecific antigens], T-cell engagers—or a class of drugs that are especially designed antibodies that bind to BCMA at one end and to a T-cell surface molecule at the other end.
Transcript edited for clarity.