ICML 2023 | AVENuE window study: avelumab monotherapy followed by PET-adapted chemotherapy approach in cHL

So I was really pleased to present the first data at ICML this year of the AVENuE study. And the AVENuE study was a UK study, it was a window study looking at four doses of avelumab, which is a PDL1 inhibitor in the frontline treatment of advanced classical Hodgkin lymphoma, followed by a response-adapted chemotherapy approach. Many of us know it as the RATHL study, so to two ABVDs, PET, PET negative four ABVDs, PET positive four escalated BEACOPP or BEACOPDac. But the question we were really asking is the safety and efficacy of those four doses of avelumab up front. So many people have looked at checkpoint inhibition before chemotherapy in frontline Hodgkin but they focused on PD1 inhibition, so nivolumab, pembrolizumab. We were interested in PDL1 inhibition, so the ligand and this is actually the first study reporting on PDL1 inhibition in that setting. We had 47 patients and we were looking for a response rate of over 40% and in fact, the response rate we had was 44%, so it was a positive study. There were some immune-related reactions, as you would expect, colitis, pneumonitis, thyroid disturbances. So there are toxicities of checkpoint inhibitors, as we know, and a key secondary endpoint was deliverability of subsequent chemo. And in fact we managed to get an 89%, chemotherapy cycles were delivered on time, which was exactly the same as the RATHL study, so that’s reassuring. And we had a one-year progression-free survival of 100%, which was great, although there have been two relapses since then. So I think my interpretation of that is it adds to the body of literature, which show that checkpoint inhibition in frontline Hodgkin leads to very high and durable remission rates. And actually we saw a randomized study, the SWOG study presented comparing AVD-brentuximab with AVD-nivolumab showing superiority in a one-year progression-free survival. So quite an early time point of AVD-nivolumab, so I’m sure we’re going to see more use of checkpoint inhibitors upfront.