COMy 2021 | Overcoming BCMA loss in myeloma cells
While BCMA is a highly efficacious target for multiple myeloma treatments, evidence is mounting that a proportion of patients treated with BCMA-directed agents will develop irreversible resistance to these therapies, attributable to biallelic BCMA loss. Hermann Einsele, MD, FRCP, University of Würzburg, Würzburg, Germany, discusses alternative targets and therapies being developed against them. For example, talquetamab is a first-in-class investigational bispecific antibody targeting GPRCD5 and CD3, and cevostamab is a novel FcRH5xCD3 bispecific antibody shown to be highly active in early clinical trials. This interview took place during the 7th World Congress on Controversies in Multiple Myeloma (COMy), 2021.
Transcript (edited for clarity)
One of the issues that we clearly have is that, there is a proportion of patients now reported, probably around 5% of patients that are showing irreversible loss of BCMA on the myeloma cell. Which is probably, mainly to a biallelic deletion of a part of the chromosome 16, which is encoding for the BCMA protein. And thus in these patients, we definitely need additional targets, and there are additional targets like GPRC5D, which is targeted by the bispecific antibody talquetamab, and they are also CAR T-cells now being produced targeting GPRC5D...
One of the issues that we clearly have is that, there is a proportion of patients now reported, probably around 5% of patients that are showing irreversible loss of BCMA on the myeloma cell. Which is probably, mainly to a biallelic deletion of a part of the chromosome 16, which is encoding for the BCMA protein. And thus in these patients, we definitely need additional targets, and there are additional targets like GPRC5D, which is targeted by the bispecific antibody talquetamab, and they are also CAR T-cells now being produced targeting GPRC5D. In addition, we have the bispecific antibody cevostamab, which is targeting FcRH5, which is an additional target on the myeloma cell. And actually this bispecific antibody was already used successfully in patients that failed treatment targeting BCMA. And finally, there are also other CAR T-cell products targeting for example, SLAMF7 or CD38, that can also be used in patients that are no longer responding to BCMA-directed therapy.
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