ASH 2025 | The evolving paradigm of frontline DLBCL treatment: strategies being explored in trial

I think we’ll have a bit of a complicated situation in the next couple years with several ongoing frontline studies with large cell lymphoma. So if we just break it into two sort of cohorts, we have our standard risk patients, usually generally 75 or younger, sometimes up to 80. We know we have the POLARIX study with Pola-R-CHP. We have more data indicating some benefit of that, potentially over standard of care R-CHOP. But on top of that, ideally, what we’ll see in the next several months to years is readouts of the ESCALADE study, which uses acalabrutinib plus R-CHOP in patients with non-germinal center large cell lymphoma. We’ll have the frontline study, which is the study of R-squared R-CHOP versus R-CHOP in patients with frontline large cell lymphoma. And then we’ll have several bispecific studies, some using R-CHOP as a platform, others using Pola-R-CHP. So when all this reads out, we’ll have to make some sort of sense of what sort of benefit we’re getting in this patient population, what are the costs because of additional treatments, timing for the patients, and what is the ideal frontline regimen for patients with large cell lymphoma, so it’ll be a bit of a complex situation. On the flip side, if we look into these elderly, unfit patients, as of right now, we don’t have a true standard of care; most people are using R-mini-CHOP in this patient population, but ideally, we know it’s not an ideal chemotherapy situation for these patients. So at this ASH meeting, we have several frontline studies utilizing bispecifics, bispecifics plus ADCs, in this patient population, and so we’re very excited to see how the data reads out and whether these will actually lead to any formal phase three studies of studying these agents versus R-mini-CHOP in this patient population.

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