New CAR-T Cellular Therapy Options for Multiple Myeloma
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Multiple myeloma is an incurable hematological cancer caused by the excessive proliferation of plasma cells. Although some patients respond to traditional therapies, many end up with numerous relapses and very few treatment options. The two most recently approved cellular therapies take aim at multiple myeloma with the hope of improving outcomes for challenging cases. These cellular therapies, called chimeric antigen receptor T cells (CAR-T cells), use genetic engineering to enhance the patient’s own T cells, helping them recognize and remove the cancer. Baylor University Medical Center at Dallas (Baylor Dallas), part of Baylor Scott & White Health, is an experienced leader in using CAR-T cell therapies — both in research and clinical care. Information about the combined expertise of Baylor Dallas and Texas Oncology to deliver advanced cellular therapies can be found at CellularTherapies.com.
A New CAR-T Therapy Produces Deep and Durable Remission
The newest CAR-T product to receive FDA approval is ciltacabtagene autoleucel (cilta-cel), a treatment for adults with relapsed or refractory multiple myeloma who have received four or more lines of prior therapy. Approved in February 2022, this treatment distinguishes itself from some other CAR-T products because it targets B-cell maturation antigen (BCMA) instead of CD19.
According to Yair Levy, MD, medical director of hematologic malignancy research and hematologist/oncologist on the medical staff at Baylor Dallas, “The amazing thing about cilta-cel is that they are seeing response rates close to 100%, and most of the responses appear durable. Safety profiles appear to be improved as well. This is a very impressive CAR-T product.” In the Phase 1b/2 CARTITUDE-1 trial of patients with relapsed or refractory multiple myeloma, the overall response rate was 97.9% with a stringent complete response rate of 78%. The median duration of response was 21.8 months at a median follow-up of 18 months.
The approval of cilta-cel follows the approval of another BCMA-targeted CAR-T product, idecabtagene vicleucel (ide-cel), in March of 2021. Dr. Levy says, “These are both excellent CAR-T products targeting slightly different epitopes. However, ide-cel has suffered from manufacturing delays, highlighting the need for multiple options on the market.”
In collaboration with Baylor Scott & White Research Institute (BSWRI), the research wing of Baylor Scott & White Health, physician-researchers at Baylor Dallas are participating in the clinical trials studying the latest CAR-T cell therapies, including the KarMMa-3 trial of ide-cel.
The Future of Therapy for Multiple Myeloma
Dr. Levy highlights the potential promise of new therapies like cilta-cel, “When we look at other treatments for late-line myeloma, we see drugs with response rates of one in four or one in three. The responses tend to be partial remissions. Given the deep and durable responses to BCMA-targeted CAR-T products, we have to start wondering if these CAR-T products can be introduced earlier. Do we need to keep putting people through so many lines of treatment?”
He also places CAR-T therapies in the context of other treatments in development. “We have other options in the pipeline like bispecific monoclonal antibodies. None are commercially approved for myeloma, but there is the potential for very high response rates. They differ from the CAR-T therapies in that they have to be given continuously, whereas the CAR-T cells are given only once. It is not clear which will be the better treatment, but we are in a very exciting time for therapeutic advances that could radically change the way we treat multiple myeloma.”
