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IMS 2024 | Antigen loss in patients with myeloma receiving immunotherapy
Mehmet Samur, PhD, Dana-Farber Cancer Institute, Boston, MA, discusses clonal evolution in patients with multiple myeloma (MM) receiving immunotherapies, such as those targeting GPRC5D or BCMA. Dr Samur explains that antigen loss occurs in a small fraction of patients, leading to the enrichment of clones with an antigen-negative phenotype, and highlights the importance of tracking these patterns to adapt treatment. Additionally, he comments on the shift toward understanding static evolution patterns. This interview took place at the 21st International Myeloma Society (IMS) Annual Meeting, held in Rio de Janeiro, Brazil.
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Transcript
The immunotherapies like therapies targeting BCMA or GPRC5D is actually one of the fields where we see a very clear clonal evolution if there is an antigen loss. When patients, which is we still as of today believe this is a small fraction of patients, maybe 5 to 10 percent, but when they lose the antigen that is targeted by immunotherapies, there is definitely a clear enrichment for a clone with the antigen negative phenotype...
The immunotherapies like therapies targeting BCMA or GPRC5D is actually one of the fields where we see a very clear clonal evolution if there is an antigen loss. When patients, which is we still as of today believe this is a small fraction of patients, maybe 5 to 10 percent, but when they lose the antigen that is targeted by immunotherapies, there is definitely a clear enrichment for a clone with the antigen negative phenotype. When this happens, we can actually track this evolution pattern and then for the subsequent immunotherapies we can try avoid using other treatments targeting the same protein and then we can switch to alternative ones. But again, this is a small fraction of patients in these patients when sometimes the relapse happens it can happen also by their microenvironment cells. It doesn’t mean that they would lose the antigens or sometimes a similar genetic background myeloma cells with maybe more aggressive phenotype can evolve. In that particular case, now the field is also moving towards understanding the static evolution patterns. In other words, when the DNA remains same, how can we learn from their transcriptome and find alternative paths to approach these patients and understand their genomic alterations.
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