EHA 2022 | ECHELON-1 trial updates: overall survival data

We had some very interesting data on ECHELON-1 presented at EHA, it had already been presented at ASCO, and this was focusing on the overall survival data. The surprise there, and it was a surprise to me, some people are saying it wasn’t a surprise to them, but it was a surprise to me, is that there is now an overall survival advantage appearing. Now, we heard this in a press release some months ago, and I think everyone wanted to know, well, what were the deaths? Because we have seen trials present an overall survival advantage, and actually, it seems to have been driven by quite random events like accidents or suicides, things unrelated to the treatment. And with Hodgkin, of course, there are very few deaths, thankfully, so you only need a fairly minor imbalance in the arms, sometimes through fairly random things, to actually generate a statistically significant difference. So we were all waiting to see that data.

But actually, I was very reassured that the overall survival difference was driven by mainly Hodgkin events or complications of treatment, and very interestingly as well, by second malignancies. In the ABVD arm, we saw quite an excess of particularly hematological malignancies, and particularly non-Hodgkin lymphomas. Now, I wouldn’t have predicted that, but it was there. I think there were 11 cases in the ABVD arm and only one case in the A-squared VD arm, so it does seem to be a real overall survival difference.

Now, the big sort of debate in the UK is six courses of ABVD, which was their control arm, is not standard of care. Most people, if they’re using ABVD would do an interim PET, and if they’re PET-negative after two cycles, they drop the bleomycin, if they’re PET-positive, not every center, but many centers would escalate to escalated BEACOPP. And with that as the control arm, would you still see an overall survival advantage with A-squared VD? Of course, we’ll never know because that trial hasn’t been done.

And so the question for us in England, because we don’t have this A-squared VD reimbursed, is, will now Takeda take this through NICE? And will they be able to get the cost per QALY, which is the metric that NICE looks at, below that magic £30,000 mark? If they do, it would be wonderful to have it available. Because even though I’m quite a fan of using more intensive approaches in younger high-risk patients like escalated BEACOPDac, there is a cohort of patients who are 45, 50, 55, 60, who I wouldn’t give that to. And if they have high-risk disease, I’d much rather use A-squared VD now than an ABVD-based approach based on that data.