iwNHL 2025 | The potential to personalize treatment based on molecularly defined subsets in DLBCL

So one of the things that we’ve found in terms of looking at the DNA-based genetic heterogeneity in diffuse large B-cell lymphoma, and part of the reason that we think it’s applicable clinically, is that there are clearly differences in the outcome using state-of-the-art standard therapy in patients who fall into the different five major categories. And so there are a couple of categories where the results seem to be consistently more favorable, and this is with several different independent groups who’ve captured this heterogeneity. And in contrast, there are a couple of groups that have a distinctly less favorable outcome. And so the idea is that by understanding and being able to identify the patients who have a less favorable outcome, and then also understanding the biology of the genetic signature and how you might think about developing more targeted therapies based on an understanding of biology, there’s the idea that you may be able to improve the treatment. And in some of our more recent work, that’s what we think we’re seeing in a preliminary way that, for instance, a targeted agent, the CD79b immunoconjugate that was part of the experimental therapy that was evaluated in the POLARIX clinical trial seems to be associated with a selective and really quite dramatic benefit in a group of tumors that we call the C5 tumors that have a particularly poor outcome with standard therapy. So that’s an example of a situation where by identifying a subtype of patients based on their genetic signature, you might be able to apply a recently approved targeted agent that could really result in a benefit to them.

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