A roundtable discussion, moderated by Thomas Martin, MD, of the UCSF Helen Diller Family Comprehensive Cancer Center, focused on CAR T-cell therapy considerations in the treatment of multiple myeloma, including data on approved CAR-T options and a look at the pipeline. Dr. Martin was joined by a panel that included Sagar Lonial, MD, FACP; Peter Voorhees, MD; and Shambavi Richard, MD.
In the first segment of the roundtable series, the panel discusses BCMA as an important target for treating multiple myeloma.
Dr. Martin: This is our first roundtable discussion on BCMA-targeted chimeric antigen receptor (CAR) T-cell therapy. We are here today to discuss CAR T-cell options in multiple myeloma. As you guys know, in the last few years, we’ve seen amazing progress in BCMA therapeutics at all our centers, and we’ve had to adjust and actually pivot and be able to incorporate these BCMA therapeutics into our practices. Today we’re going to discuss your experience with some of these therapeutics. It’s actually been a really fun time. The first thing I want to discuss is why BCMA? BCMA has now really come onto the scene as a major player in terms of targets for multiple myeloma. I think we’ve enjoyed our time with CD38, and now we’re on BCMA. Dr. Lonial, why BCMA in multiple myeloma?
Dr. Lonial: BCMA, to me, is almost the ideal target in the sense that BCMA biologically is responsible for many of the bad things malignant plasma cells like to do. Binding through BCMA induces signaling through a number of pathways that ultimately result in drug resistance, proliferation, and binding to the stroma in the marrow, which we know confers some level of drug resistance in and of itself. While BCMA is a good flag on the surface of a myeloma cell to target, targeting BCMA purely from a biologic perspective probably does a number of things that many of our other immunologic targets such as SLAMF7 or CD38 biologically don’t seem to be able to do. It’s almost a two for one. You get a great target, but you also interrupt survival signaling through the BCMA receptor.
Dr. Martin: In your experience, have you seen any on-target but off-tumor side effects from people getting BCMA-directed therapy?
Dr. Lonial: I think we do know, and I know we’re going to talk about this as well, that BCMA expression is not uniquely limited to plasma cells. It is on other B-cell progenitors in the lineage. You do get some immunosuppression, if you will, by eliminating BCMA, depending upon how effective your drug is in earlier lines or stages of B cells. I think much of the cytopenias that we often see after highly effective BCMA-directed therapy likely is a local bystander effect on the normal marrow when you’re coming in with a really effective T cell or T-cell engager in that context.