Assessing CAR T-Cell Therapy With Novel Targets for R/R Multiple Myeloma
Omar Nadeem, MD, clinical director, Myeloma Cellular Therapies, Dana-Farber Cancer Institute, discussed GPRC5D-targeted CAR-T, BMS-986393.
Omar Nadeem, MD
Credit: Dana-Farber
BMS-986393, a GPRC5D-targeted chimeric antigen receptor (CAR) T-cell therapy, was well-tolerated and yielded responses in patients with relapsed/refractory multiple myeloma and 1-to-3 lines of prior therapy, according to initial data from the phase 1 CC95266MM001 study (NCT04674813).
The data, from 31 patients were presented by Omar Nadeem, MD, medical oncologist and clinical director, Myeloma Cellular Therapies Program, Dana-Farber Cancer Institute and instructor in medicine, Harvard Medical School, at the European Hematology Association 2024 Hybrid Congress, held June 13-16 in Madrid, Spain, and virtually. The participants received 150 x 106 CAR T cells and had an overall response rate of 96%, with a complete responses rate of 32%, although median follow-up time was only 3.2 months (range, 0.5–5.8) at the time of data cutoff.
CGTLive® spoke with Nadeem to learn more about the new data, and the potential advantages of BMS-986393 in the treatment landscape of multiple myeloma. He emphasized the unmet need that remains in the space and the benefit of new CAR T-cell products, especially ones with novel targets like GPRC5D.
CGTLive: What unmet needs remain in the relapsed/refractory multiple myeloma treatment landscape, despite novel approvals?
So multiple myeloma therapy is improving quite rapidly like everyone knows in the nose, but there's still a big unmet need in patients with relapsed/refractory disease. We have numerous combinations that have been approved and we've identified T cells and bi specifics for patients with relapse after these therapies, particularly BCMA-targeted therapies. So, there's an unmet need there to be able to offer these patients effective technologies.
There's definitely an unmet need for additional therapies in relapsed/refractory multiple myeloma, and particularly a need for additional CAR T-cell therapies. Right now, we do have 2 BCMA-directed CAR T-cell products approved for myeloma, but they're hindered by limited availability and supply and logistical concerns to be able to treat all the patients that need these therapies. So, despite having 2 products, we are not able to treat all the patients that require CAR T-cell therapy. And more CAR T cell products are necessary, particularly the ones that have a different target than BCMA.
GPRC5D is a new target that has been discovered on the surface of plasma cells and myeloma cells. We do have a therapy approved that targets GPCR5D, a bispecific antibody called talquetamab whichhas pretty good efficacy but concerns when it comes to toxicities. And what we have here is a GPRC5DCAR T-cell targeting product that is hoping to mitigate some of the toxicity concerns, which is something we've seen with CAR T-cell products compared with bispecific antibodies.
What is ongoing research with BMS-986393 looking to answer?
So far, we're very encouraged with the toxicity and efficacy profile we're seeing with this GPRC5D-targeting agent.The question is, where would this fit into the myeloma treatment landscape? As I mentioned, we have other GPRC5D targeted bispecific antibodies approved, but they're not necessarily approved after BCMA-targeting therapies, so very few patients in this cohort that had 1-to-3 prior lines of therapy actually had prior BCMA-targeted therapy. But there are other results in the additional cohorts. We definitely see activity in the outpatient population. So, this could be a great option, either before or after prior BCMA-directed therapy.
We also have ongoing trials of looking at this in a phase 2 trial, looking at efficacy of this agent in a larger patient population, and then also looking at different combination therapies; and in another phase 1 trial with some of the agents that are currently under investigation in multiple myeloma for some anticipated combination therapy data.
This transcript has been edited for clarity.
