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ASH 2025 | Enhanced T-cell fitness in high-risk smoldering vs R/R myeloma with bispecifics and CAR-T
Irene Ghobrial, MD, Dana-Farber Cancer Institute, Boston, MA, discusses single-cell immune profiling showing superior immune fitness of both endogenous and engineered T-cells in patients with high-risk smoldering myeloma compared with those treated in the relapsed/refractory (R/R) setting. She explains the potential benefit of earlier use of bispecific antibodies and CAR T-cell therapies by leveraging a more intact immune system. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
We’ve looked at immune single cell sequencing from smoldering multiple myeloma patients who were treated on our bispecific clinical trials with teclistamab or with CAR-T therapy, or we looked at patients with exactly the same drugs, teclistamab or cilta-cel, in relapsed refractory setting. And we wanted to ask the question, is the immune system important to really make a difference in your response and your resistance to therapy? And is that coming from the T cells that you take out and engineer in a CAR-T? Or is that really the endogenous T cells in your body? And the earlier you have those patients, like in smoldering myeloma, the better...
We’ve looked at immune single cell sequencing from smoldering multiple myeloma patients who were treated on our bispecific clinical trials with teclistamab or with CAR-T therapy, or we looked at patients with exactly the same drugs, teclistamab or cilta-cel, in relapsed refractory setting. And we wanted to ask the question, is the immune system important to really make a difference in your response and your resistance to therapy? And is that coming from the T cells that you take out and engineer in a CAR-T? Or is that really the endogenous T cells in your body? And the earlier you have those patients, like in smoldering myeloma, the better. And indeed, we will be showing here in ASH that it matters a lot what kind of immune system you have before you receive a bispecific or before you receive a CAR T. And in patients with smoldering myeloma, where they have a better T cell fitness, indeed, not only their CAR T cells are better and more effective, but also their endogenous T cells, the ones that are resident in the bone marrow, are much more effective in killing the myeloma cells. That gives us so much information that, indeed, not every patient will benefit from a bispecific or a CAR-T in heavily pretreated relapsed refractory myeloma. And the earlier, the better for our patients. And also ask the question of, should we be then collecting T cells earlier for our patients?
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