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BSH 2022 | Updates from the AVENuE trial: avelumab for advanced classical HL

In this video, Graham Collins, MA, MBBS, MRCP, FRCPath, DPhil, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, shares some insights into the AVENuE trial (NCT03617666), which is investigating the use of the PD-L1 inhibitor avelumab for the frontline treatment of advanced classical Hodgkin lymphoma (HL). Dr Collins first explains the treatment approach used in this trial, as well as the main aims of this trial. Following this, Dr Collins highlights the growing interest in the use of checkpoint inhibitors upfront, and the hope that the addition of checkpoint inhibitors in HL treatment results in a reduction in chemotherapy burden in patients. This interview took place at the 62nd Annual Scientific Meeting of the British Society for Haematology (BSH) 2022, in Manchester, UK.

Transcript (edited for clarity)

So the AVENuE trial is looking at integrating checkpoint inhibitors into the frontline treatment of classical Hodgkin lymphoma. It’s actually the only trial that’s looking at a PD-L1 inhibitor, avelumab. And so it’s taking patients with either early unfavorable or advanced stage disease, it’s treating patients with four doses of avelumab every two weeks, and then every patient goes onto ABVD and follows a RATHL approach, so two ABVDs, interim PET, four AVDs if it’s negative, or escalated BEACOPP or BEACOPDac if it’s positive...

So the AVENuE trial is looking at integrating checkpoint inhibitors into the frontline treatment of classical Hodgkin lymphoma. It’s actually the only trial that’s looking at a PD-L1 inhibitor, avelumab. And so it’s taking patients with either early unfavorable or advanced stage disease, it’s treating patients with four doses of avelumab every two weeks, and then every patient goes onto ABVD and follows a RATHL approach, so two ABVDs, interim PET, four AVDs if it’s negative, or escalated BEACOPP or BEACOPDac if it’s positive. And what we’re really hoping to show is that … well, what I’m really hoping to show actually is that there’s some sort of chemosensitization here. So for patients who have that avelumab, I’m really hoping that we see a low rate of interim PET positivity. So are we benefiting patients by making their chemotherapy more effective?

47 patients was our sort of recruitment ask. And we’ve given out all of the patient information sheets now. We’re just waiting to hear if the final few patients are going to be registered on study, and then it’ll be a bit of a wait to get the data. I’m hoping we might have it ready possibly for ASH this year; if not, probably Lugano next year. And that’ll be really exciting, because there’s a lot of interest looking at checkpoint inhibitors upfront. I think you mentioned the trial in the US comparing AVD brentuximab with nivolumab AVD. That’s an ongoing study. The problem with that study … I mean, it’s a really good study. And I think we are all very excited to see the results. But A2VD is not a standard of care in this country, so it’s just not funded. So how relevant that study is to our practice is a bit difficult to say.

And what I really hope actually we see with checkpoints inhibitors upfront is, okay, we could just add it into chemo and hope we make the chemo a bit better. Sure. I mean, that’s a worthy aim. What I really hope we can do actually is use them to reduce the chemotherapy burden, because six cycles of AVD, that’s 300 milligrams per meter squared of doxorubicin, that has a significant cardiac toxicity burden. And we are increasing late effects risks to our patients, ischemic heart disease, et cetera. So to actually use these agents to reduce the chemotherapy burden I think is the way we really need to be going with these agents upfront. And once we’ve got the AVENuE data, I’m hoping we’ll be able to design trials where we actually do that. Perhaps we take the really good responders to checkpoint inhibitors and actually give them less chemo upfront, rather than just giving them the same that they would otherwise always get.

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Disclosures

Honoraria: Roche, Takeda, Gilead, Pfizer, MSD, Celleron, ADC Therapeutics, Incyte, Beigene. Research funding: BMS, MSD, Celleron, Amgen, BMS