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The 2022 Tandem Meetings | Latest advances in CAR-T for multiple myeloma: cilta-cel & new CAR-T platforms

Mahmoud Gaballa, MD, Massachusetts General Hospital, Boston, MA, shares the most exciting developments in CAR-T therapy for multiple myeloma. There are currently two CAR-T products approved by the FDA, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). These approvals were based on the results of the KarMMa (NCT03361748) and CARTITUDE-1 (NCT03548207) trials respectively. Multiple promising CAR-T platforms are being developed in pre-clinical or early phase studies, including ARC-T cells, T-Charge, fully humanized CAR-Ts, and CAR-Ts targeting non-BCMA antigens. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT™ and CIBMTR® 2022 in Salt Lake City, Utah.

Transcript (edited for clarity)

There are a lot of advances when it comes to CAR-T therapy in multiple myeloma. The first product that was approved is ide-cel, or Abecma, and it was approved based on the KarMMa trial, which had shown an overall response rate of 82% at the highest dose level with a medium PFS of 8.6 months and a median OS of 24.8 months. And then earlier this year in 2022, another CAR-T product, cilta-cel, was also approved and it also targets BCMA, but it targets two different epitopes...

There are a lot of advances when it comes to CAR-T therapy in multiple myeloma. The first product that was approved is ide-cel, or Abecma, and it was approved based on the KarMMa trial, which had shown an overall response rate of 82% at the highest dose level with a medium PFS of 8.6 months and a median OS of 24.8 months. And then earlier this year in 2022, another CAR-T product, cilta-cel, was also approved and it also targets BCMA, but it targets two different epitopes. The results were very promising based on the CARTITUDE-1 clinical trial that showed an overall response rate of 97.9% and 18-month PFS of 66% and 18-month OS of 80.9%.

And then the pipeline of products available, there is a plethora of products being developed and investigated. Here, MGH actually developed a novel product called Tri-APRIL, which is based on a trimeric APRIL approach, and it targets both BCMA and TACI, and it’s thought to have improved outcomes and to mitigate the risk of BCMA-negative relapse.

Another exciting development is a platform called ARC-T cells combined with SparX proteins. It’s a platform and it allows controlling response by controlling the dose of the SparX proteins, and it also allows to adapt to the tumor as it changes its antigen expression over time.

Another exciting development, which is currently in early phase clinical trials, it’s a technology called T-Charge and a clinical trial PHE885, where there is rapid manufacturing and in vivo expansion occurs, so the vein-to-vein time is around 7 days and the early results presented at recent national conferences are actually very promising. And lastly, there are other approaches being pursued. There are fully humanized CAR-T products and there are other products that target non-BCMA antigens. So, overall, there is a lot of developments in this field and it’s exciting times.

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