Non-BCMA CAR T-Cell Therapy Shows Promise for the Treatment of Relapsed/Refractory Multiple Myeloma
Syed Maaz Tariq, MD, White River Medical Center, Batesville, Arkansas, discusses the results from a retrospective meta-analysis which evaluated non-BCMA chimeric antigen receptor [CAR] T-cell options for patients with relapsed/refractory (R/R MM).
The results of this analysis demonstrated efficacy and safety for GPRC5D, a non-BCMA CAR T-Cell therapy, for patients who have R/R MM, and, Dr Tariq stated, “It is an interesting topic with room to open more avenues for physicians and for oncologists to consider. There is increased room to have more results and more exciting results for our patients in the future.”
Transcript:
My name is Dr Syed Maaz Tariq and I'm PG1 [Post-Graduate Year 1] internal medicine resident at White River Medical Center in Batesville, Arkansas. Today I'm here to talk about my abstract at ASCO 2025, about non-BCMA CAR T-cell therapy for multiple myeloma.
As we all know that CAR T-cell therapies have changed the landscape of cancer therapeutics, and they offer us physicians another line to treat refractory and relapsed multiple myeloma in patients who have at least 4 lines of therapy. For multiple myeloma, we have two currently FDA approved CAR T-cell therapies such as ciltacabtagene autoleucel and idecabtagene vicleucel. These therapies target the B-cell maturation antigen on the multiple myeloma cells. For now, this is the only target we have. As we have seen through multiple clinical trials, these therapies, the BCMA-targeted CAR T-cell therapies, they provide deep response, but it has been observed that eventually later in the course there is a disease relapse, and patients become resistant to these therapies. With these problems in mind, there has been ongoing scientific work on finding newer targets and the most sought-after targets currently are GPRC5D, SLAMF7, CD38, CD138, and CD229. In our meta-analysis we went about searching for studies that are investigating non-BCMA CAR T-cell therapies.
What we found, we had only 3 studies done in the time 2022 to 2023 and all of them, interestingly were investigating GPRC5D treatments. We had 60 patients in all 3 studies combined, and most of them, almost half of them, I would say they had high risk cytogenetics. There were highly encouraging findings such as the overall response rate was 89.1%. Interestingly, a very low mortality rate of 0.8%.
As far as our side effect profile is concerned, most of them had neutropenia, which was kind of an expected side effect because of the nature of these treatments as they were targeting antigens on the cell surface. Another salient feature of our study was that only 1 study mentioned progression-free survival, which was 87.5%. If we talk about the fact that we only had 3 trials, which are investigating non-BCMA CAR T-cell therapies, we as a group, we highly believe that this is an ongoing discussion. As newer trials are published, there is a lot of room to extend this study. We can do a follow-up study on adding more clinical trials as years go by and as we have more trials.
Interestingly, a lot of ongoing studies are currently investigating bispecific antibodies. They're not targeting only 1 antigen on the cell surface, they're targeting 2. These trials, when they have resulted, they can give us an in-depth picture. For example, bispecific CAR T-cell therapies in multiple myeloma is a trial which is investigating in BCMA and CD19 dual targeting CAR T-cells. In the phase 1 trial, the overall response rate was found to be 93.1% and with 82.8% patients having a stringent complete response. There are other few studies that are targeting BCMA and CD38. Other few studies they have been targeting BCMA and GPRC5D together.
It is an interesting topic with room to open more avenues for physicians and for oncologists to consider. There is increased room to have more results and more exciting results for our patients in the future.
Source:
Tariq SM, Khalid MF, Noor J, et al. Outcomes with non-BCMA CAR T cell therapy for multiple myeloma: A systematic review and meta-analysis. Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract e19541.
