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ASH 2021 | Novel agents in the post-BCMA space in myeloma

BCMA is an effective treatment target for multiple myeloma as a result of its selective expression on malignant plasma cells. BCMA-targeted immunotherapy has proved highly efficacious in clinical trials of several different agents, including bispecific T-cell engagers (BiTEs), CAR T-cells, and antibody-drug conjugates. Consequently, belantamab mafodotin and idecabtagene vicleucel, two BCMA-targeting agents, have recently been approved for use in relapsed/refractory multiple myeloma. Noopur Raje, MD, Massachusetts General Hospital, Boston, MA, discusses the importance of developing options for the post-BCMA space. GPRC5D and FcRH5 are novel targets that have shown promise. Data regarding talquetamab and cevostamab, bispecifics targeting GPRC5D and FcRH5, respectively, will be shared at the ASH 2021 annual meeting. Dr Raje comments on where novel agents like these are likely to fit into the myeloma treatment paradigm. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.

Transcript (edited for clarity)

So, you are going to hear a lot of this at this year’s ASH, because, first of all, with BCMA targets, we’ve talked about CAR-T cells, there are other CAR-T cell products, which are going to be presented that this year’s ASH as well, but then there are the bispecific T-cell engagers, and there’s a whole host of bispecific T-cell engagers which are targeting BCMA. Those will be presented...

So, you are going to hear a lot of this at this year’s ASH, because, first of all, with BCMA targets, we’ve talked about CAR-T cells, there are other CAR-T cell products, which are going to be presented that this year’s ASH as well, but then there are the bispecific T-cell engagers, and there’s a whole host of bispecific T-cell engagers which are targeting BCMA. Those will be presented.

And there’s a couple of other targets that we are interested in, and you’re going to see data with CAR-T cells as well as with bispecifics, and specifically the two bispecific T-cell engagers include talquetamab, and the other one is cevostamab. So talquetamab targets GPCR5, and there’s a CAR-T cell product against this as well with really high response rates, an excess of 70%. And then there’s another bispecific T-cell engager targeting FCRH5, and with that, this is cevostamab, and there’s data being presented at this year’s ASH with cevostamab as well, and the data with this shows a response rate of an excess of 50%, close to 60%. And this is in patients who’ve been exposed to a BCMA-targeted agent. So there is life beyond BCMA, which will be presented at this year’s ASH meeting.

BCMA, obviously, is a great validated target, but we are still seeing relapses post-BCMA. So we have to start figuring out what the post-BCMA space is going to look like, and for us to have drugs like talquetamab and cevostamab are great. So targets of GPCR5, as well as targeting FCRH are good things, specifically for post-BCMA relapses. I do think they’re going to sort of be used sequentially, because the data so far suggests a slightly lower response compared to BCMA. But the future would also be looking at maybe combining some of these, so combining a BCMA target with one of these other targets, so that we get an even better response rate and more of a durability of response. So these would be things which we would consider in the future, but for right now, the fact that we are seeing high response rates with non-BCMA targets is actually an amazing thing for myeloma.

 

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