ASH 2022 | Investigating the mechanisms of initial & acquired resistance to BCMA CAR-T therapy in myeloma
Mehmet Samur, PhD, Dana-Farber Cancer Institute, Boston, MA, discusses a study that explored the immune and microenvironmental factors that drive resistance to CAR-T therapy in patients with multiple myeloma. The study showed that initial and acquired resistance appeared to be driven by different factors. This interview took place at the 64th ASH Annual Meeting and Exposition congress in New Orleans, LA.
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Transcript (edited for clarity)
In terms of using single-cell technologies to understand the resistance to anti-BCMA therapies, we have seen differences from initial responders to patients who don’t have initial response, mainly on the plasma cell characteristics or their multiple myeloma cell characteristics. When we look at their microenvironment, as we have been looking at these from many different angles, we did not see a real difference in terms of T-cell functionalities or in terms of microenvironmental differences, so they were very similar to each other...
In terms of using single-cell technologies to understand the resistance to anti-BCMA therapies, we have seen differences from initial responders to patients who don’t have initial response, mainly on the plasma cell characteristics or their multiple myeloma cell characteristics. When we look at their microenvironment, as we have been looking at these from many different angles, we did not see a real difference in terms of T-cell functionalities or in terms of microenvironmental differences, so they were very similar to each other. However, their myeloma cells or their plasma cell structure was looking quite different. And then we took this study further and then looked at the cells from the same patients before treatment and then after treatment. That was the main component where we have started to see changes on the microenvironment cells.
That basically led us to the point that maybe initial response and then resistance basically acquired after initial response are driven by different factors or multiple factors. I think with the data accumulation over the years now, we are beginning to understand these patients in a much better way. With some of these treatments now commercially being available, the data pools are getting bigger, and that gives us more flexibility to break down the patient populations and understand the real resistance mechanisms at different stages.
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