ASH 2024 | Genomic determinants of resistance to anti-BCMA CAR-T therapy in patients with R/R myeloma

So in this study that we developed together with the Moffitt Cancer Center Insititute, University of Calgary and Memorial Sloan Kettering, we sequenced for the first time a large series, or relatively large, of 74 patients with multiple myeloma treated with anti-BCMA CAR-T therapy. And what we found is that whole genome sequencing, so the simple DNA genomic profiling identifying which alterations are different between the tumor and the normal, allow us to basically identify all the patients that progressed, all the patients that did not respond, like the refractory, the ones that after 100 days are still with a lot of disease, and we also identify patients that have a great response, like many years of remission. And that makes a lot of sense biologically, and what we found is that these alterations are often genomic instability that allow the loss of alterations that makes the plasma cell less plasma cell, so reducing BCMA or have a better capability to escape BCMA therapy. What is interesting is that some of these patients can respond to other therapies because it’s more BCMA-driven and so maybe other therapies can work better. So what we think and the big idea behind this research pipeline is to identify alterations that guide our decision. And so if you have a certain mutation, you get the GPRC5D. If you get another mutation, you get the BCMA. And I think it’s really possible. And also I like the importance of genomic profiling, not just at diagnosis, but in different phases of therapy to really understand which is the best therapy we want to give.

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