COMy 2021 | Treating multiple myeloma resistant to BCMA-targeted therapy

So it has now been described, in a subset of patients that received CAR T-cell therapy, that resistance was caused by biallelic deletion of the BCMA gene. So these patients have loss of BCMA, total loss of BCMA and thereby they fail BCMA-targeted therapy. These patients can benefit from a GPRC5D-targeting treatment like the bispecific talquetamab, or from a FcHR5-targeted therapy like cevostamab.

Maybe better is to combine agents that target different antigens, so that you prevent the development of these escaped variants. So at this moment, indeed, several studies are evaluating the combined targeting of two different antigens. For example, teclistamab or talquetamab can be combined with daratumumab, a CD38-targeting agent. There is also a study ongoing where teclistamab and talquetamab are combined. So targeting BCMA and GPRC5D at the same time.

And in the CAR T-cell field, there is also a lot of progress where CAR T-cells are being developed that can target two different antigens at the same time, because these CAR T-cell have, for example, a CAR that has two different antigen binding parts, for example, one binding CD38, and one part binding BCMA. And some of these products are also now being evaluated in clinical studies. So in the next months, years, we will learn much more about targeting two antigens at the same time to induce deeper responses and at the same time, also induce, more durable responses.