General Updates | How the Hodgkin lymphoma treatment landscape has evolved: BV-AVD, nivolumab-AVD, BrECADD & more

So over the last 10 or so years, we’ve seen a very interesting development of the treatment of frontline Hodgkin lymphoma, particularly for advanced stages. We’ve had, of course, ABVD and escalated BEACOPP for quite a while. And I think with the HD18 results, so that’s a PET-adapted trial done by the German Hodgkin study group, whereby they gave patients two cycles of escalated BEACOPP and then a PET scan. And if the PET scan was negative, they only had another two and if it was positive they had another four that really did start changing practice because it showed that a PET-adapted approach was actually just as good as a non-PET-adapted approach where everybody got six so that meant that actually patients on an escalated BEACOPP program were getting about 90% cures but most of them were only having four cycles that’s over in three months it’s quite a low anthracycline dose and that probably led to more use of a more intensive regimen, particularly in the UK. It’s been standard of care for some time now in quite large parts of continental Europe. In the UK, what we did was swap out procarbazine and added in dacarbazine. That was based on pediatric data. And we did a sort of rolling data collection exercise to show that it looked less gonadotoxic, as we would expect. It looked like it was a bit less toxic to the bone marrow. So, we were seeing lower rates of anemia and platelet use and red cell transfusion, but just as good outcome. So that sort of stayed the standard of care in the UK for some time. Interestingly, we’ve now seen some trials come through which are sort of reversing the concept of PET adaptation. So in the US, for example, they have not really taken on board PET adaptation in quite sort of with such enthusiasm, perhaps, as I can say, as us in the UK and continental Europe. So they actually did a study, well, it was a global study, in fact, of comparing ABVD with AVD-brentuximab. That was the ECHELON-1 study, and that was a commercial study, and that showed a benefit in terms of PFS and actually on longer follow-up in terms of overall survival of AVD-brentuximab compared to ABVD. So in certain territories where that was reimbursed, that became standard. And actually in the UK, or in England at least, we’ve actually just had NICE approval for that regimen. So I think where we would have used an ABVD approach for advanced stage disease, perhaps where fertility and other toxicity concerns were paramount, we’ll probably switch to an AVD-brentuximab approach. It’s hard to think why we would use ABVD where there’s an overall survival advantage. But we also saw something called the SWOG study. This was run by the US, where they compared AVD-brentuximab six cycles, no PET adaptation to AVD-nivolumab. And at one and two years, there was a significant progression-free survival for Nivo-AVD. The only issue I have with that study is still quite short follow-up. The median follow-up was two years. We really need to see three or preferably four-year follow-up to be confident that there is an ongoing benefit. What is most exciting, I think, about that study, though, is when you look at older patients, so perhaps 50 or 60 plus, they’re the ones who seem to really get the benefit of Nivo-AVD compared to AVD-Brentuximab. And that’s the group that we really have a sort of unmet need for in the frontline setting. So I think looking ahead, that’s where really I see its niche. Now, we have also seen developments in a PET-adapted approach. So again, the German Hodgkin’s study group took escalated BEACOPP, modified it, so introduced brentuximab, made a number of other modifications, and came up with BrECADD. And they compared escalated BEACOPP with BrECADD in the HD21 study. So again, using that PET-adaptive design, two cycles, PET negative, two more, PET positive, four more. And it was designed as a non-inferiority in terms of progression-free survival and they wanted to see a reduction in treatment-related morbidity. Well, they did see a reduction in treatment-related morbidity, albeit relatively modest, but less hematotoxicity in particular. But actually, they saw superiority. So, they showed a four-year progression-free survival of 94%, which is incredibly good. So, I think BrECADD, again, when it’s available, we don’t have that available yet in England in terms of reimbursement, but when it’s licensed and approved, will become a standard, particularly in centres which were using escalated BEACOPP or escalated BEACOPPDac. And I know it’s already a standard in parts of Europe where reimbursement is less of an issue. So, yes, some really exciting developments and making the cure rates of Hodgkin even higher than they once were.

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