DocWire News sat down with Natalie Callander, MD, professor and director of the Myeloma Clinical Program at the University of Wisconsin Carbone Cancer Center, about B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma (MM), and data on the benefits of this agent for the treatment of relapsed/refractory disease.
DocWire News: BCMA is a target of interest for MM. What makes BCMA CAR T cell therapies different from other CAR Ts for this disease?
Dr. Callander: CART T, chimeric antigen receptor T cells, are basically a concept of reprogramming a patient’s own T cells to go after various targets. Probably, the first one that was really investigated is one called CD19 and that’s actually displayed on B cells of all types. It was initially investigated in MM, but it appeared to be a relatively poor target that cells would lose CD19 and perhaps not all myeloma cells were displaying that. BCMA is more reliably expressed on plasma cells in myeloma cells; and again, the concentration of BCMA antigen on the surface of myeloma cells seems to increase as patients become more refractory. Because it’s also pretty much limited to plasma cells, that means that there are fewer off target effects, which is, again, a very nice property of these kinds of drugs. You would like to just target the myeloma cells and not other drugs or not other types of cells. BCMA fits that purpose.
DW: Do BCMA CAR T cells appear to be a beneficial therapy for patients with relapsed/refractory MM?
Dr. Callander: Well, I think that we’ve got some great data, both from the KarMMA study, as well as the CARTITUDE study. These are a slightly different CAR T products. Both of them have had very high response rates. The CARTITUDE trial was updated at [the American Society of Hematology (ASH) 2020 Annual Meeting] recently and showed a 97% response rate, which is pretty amazing and people who’ve had an average of five different types of treatment. I think that these therapies really are going to be used widely. There is going to be a limitation initially that there has to be some expertise in the facilities that are administrating CAR T just so they’re familiar with some of the side effects. Some of the side effects vary a little bit in timing, depending on the different CAR T products. But again, one of the patient advantages receiving these types of treatments is they then have a period of time when they’re actually off therapy, which many, many, many patients really enjoy.
I think with the kind of response rates and the duration of response, which seems to be quite good, particularly in those patients who obtain a complete remission, I think that these are going to be probably sought after as soon as they’re FDA approved.
I think one thing that we don’t know, just thinking about BCMA and different drugs that are out there. We do have belantamab, that’s the only drug commercially available right now that targets BCMA. There are these bio-specific engagers that target BCMA; then, there’s CAR T. One thing that we don’t know yet is how you sequence this. If you have had one BCMA therapy and it stops working, could you move to another? Or is there sort of an optimal way you move through these over time?