ASH 2024 | Predicting response and survival in patients with PTCL treated with pembrolizumab and romidepsin

One of the big questions in T-cell lymphoma is when we have a therapy, we don’t know why it works and how it works. And since our investigator initiated a study of pembrolizumab, checkpoint inhibitor with romidepsin, was conceived in 2018 and we’ve had several oral presentations at ASH, we wanted to update the data and also show the correlatives to demonstrate which patients respond and which patients don’t respond. Because it’s a checkpoint inhibitor, not all of them respond. What we did find in the previous iterations was that the response is clearly seen in the TFH subtype of T-cell lymphomas compared to PTCL and the other types. And when we took a deep dive and took the samples, pre-treatment samples, and did various analyses, whole exome sequencing, RNA-seq, the proteins by using this multiplex Codex, and also computational pathology we were able to look at the microenvironment spatially and understand how the responders do and how the non-responders do and the summary is that’s a lot of data at a single-cell level especially using Codex which identifies 126 subtypes of the T-cells, B-cells, NK-cells and we found that the responders have very high CD8s and the non-responders have high levels of myeloids and macrophages. I think it’s the balance that is also important to understand when you use a therapy why it works and why it doesn’t work and perhaps some of the strategies might be to downregulate the macrophages so that you can make this combination therapy work better. So this is a very important study and not many studies are along these lines. It’s the first of its kind in T-cell lymphoma.

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