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ASH 2025 | Immune exhaustion impacts CAR T-cell efficacy in Richter’s transformation
Frederick Locke, MD, Moffitt Cancer Center, Tampa, FL, discusses the impact of immune exhaustion on CAR T-cell efficacy in Richter’s transformation (RT). Dr Locke highlights that differences in the immune microenvironment might contribute to worse outcomes with CAR-T therapy. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
Richter’s transformation is a manifestation of chronic lymphocytic leukemia where it can transform into a faster-growing aggressive lymphoma. And it resembles diffuse large B-cell lymphoma and sometimes is treated that way. But Richter’s transformation when treated with CAR T-cell therapy doesn’t always have the same outcomes. And so we started to ask questions about the immune microenvironment in the Richter’s tumors and whether that has an impact on CAR-T outcome...
Richter’s transformation is a manifestation of chronic lymphocytic leukemia where it can transform into a faster-growing aggressive lymphoma. And it resembles diffuse large B-cell lymphoma and sometimes is treated that way. But Richter’s transformation when treated with CAR T-cell therapy doesn’t always have the same outcomes. And so we started to ask questions about the immune microenvironment in the Richter’s tumors and whether that has an impact on CAR-T outcome. And so really the first step we did was biopsies of our Richter’s transformation patients. We did limited gene set analysis and we compared those to diffuse large B-cell lymphoma patients to evaluate whether the immune microenvironments of the tumor were different between those two patient populations. And certainly, the Richter’s patients had more exhausted T-cells and more progenitor-exhausted T-cells than diffuse large B-cell lymphoma patients. And we hypothesized that that might be one of the reasons why they have worse outcomes with CAR T-cell therapy. More work needs to be done, but it’s really interesting to kind of start to understand the biology of these tumors and start to think about strategies we could use to improve outcomes.
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