Bal on Targeting GPRC5D in R/R Multiple Myeloma

GPRC5D is a receptor expressed on multiple myeloma cells and is considered a promising therapeutic target. The FDA-approved drug talquetamab (Talvey), a T-cell engager targeting GPRC5D, has shown positive results in treating relapsed myeloma. While GPRC5D's potential is present, questions remain regarding its optimal treatment approach within the evolving myeloma treatment landscape.

Susan Bal, MD, malignant hematologist and associate professor at the University of Alabama Birmingham, presented findings from a phase 1 study (NCT04674813) investigating chimeric antigen receptor (CAR) T-cell therapy as a strategy for targeting GPRC5D at the American Society of Hematology 2023 Annual Meeting. In an interview with Targeted Oncology^TM, Bal discusses the study.

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0:09 | So GPRC5D is an orphan receptor that's been described by some of the work led by Dr. Eric Smith [MD, Cellular Therapeutics Center, Department of Medicine, Memorial Sloan Kettering Cancer Center]. It's expressed on the surface of multiple myeloma plasma cells, but luckily is not very expressed on the surface of normal tissues other than certain parts of the heart keratinized tissue. It's really shown to be a promising therapeutic target for myeloma. We now have FDA approval for talquetamab as well, which is a T-cell engager targeting GPRC5D. We have data from this study and several others which show that targeting GPRC5D can be an promising therapeutic target for relapsed myeloma.

0:44 | GPRC5D overall is is a very important target in myeloma. There remain several questions about the adequate sequencing of this approach in the current landscape of all of the development that we're lucky enough to have in myeloma. But I would say that, you know, talquetamab is already approved, but we're still understanding what is the best way to target the GPRC5D receptor. In my opinion, given the differences in toxicity that we have seen, this receptor may be better targeted with a 1-time strategy of CAR T cells compared to the T-cell engagers.

1:17 | Toxicity profile seems to be a little bit different. Also, patients enjoy being off therapy. They value that. So I do think that more data to come. This is still of course early in study. We have a phase 2 study plan. We have a combination phase 1 study plan. And so as this gets closer and closer to approval, the important thing is to refer the patients early, because we have these amazing treatments that are available to their patients and we can help the greater myeloma community.