CAR-T Meeting 2024 | Antigen loss as a key driver of resistance to anti-BCMA T-cell therapies in myeloma
Paola Neri, MD, PhD, University of Calgary, Calgary, Canada, comments on antigen loss as a key driver of resistance to anti-BCMA CAR T-cell therapy and T-cell engagers (TCEs) in multiple myeloma (MM). A significantly greater rate of antigen loss is seen following TCE therapy than CAR-T, likely due to TCE therapy involving continuous treatment, not a single infusion. Dr Neri highlights that it is important to determine whether the appropriate target is present in a patient before starting therapy. This interview took place at the EBMT-EHA 6th European CAR T-cell Meeting in Valencia, Spain.
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Transcript (edited for clarity)
Today, I presented our work on the cause of resistance to CAR-T and T-cell engagers, and I kind of describe the fact that antigen loss seems to be the main driver of resistance.
We have reported that it’s happening in 6% of cases after anti-BCMA CAR-T, but 42% after T-cell engagers. And [we] got a lot of questions regarding why this difference, why [does it occur] much more after a T-cell engager therapy...
Today, I presented our work on the cause of resistance to CAR-T and T-cell engagers, and I kind of describe the fact that antigen loss seems to be the main driver of resistance.
We have reported that it’s happening in 6% of cases after anti-BCMA CAR-T, but 42% after T-cell engagers. And [we] got a lot of questions regarding why this difference, why [does it occur] much more after a T-cell engager therapy. And I think the answer is that we continue this therapy with the T-cell engager, while with the CAR-T it is just a one-time event. So, I think the cause of resistance is more frequent because we continue therapy, so we select maybe some clones that are present, and then they emerge because the other cells are actually reduced. And I was just describing the main genomic event that caused resistance in terms of antigen loss, and one can be biallelic loss or monoallelic loss and the presence of mutation in the extracellular domain of BCMA.
So my take home is the fact that we really need to pay attention to that, because we have so many options for myeloma so we need to know if the target is there before even starting therapy.
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Disclosures
Consultancy: Janssen, BMS, Pfizer, Sanofi; Honoraria: Janssen, BMS, Pfizer, Sanofi.
