ASH 2025 | Incorporating novel agents in frontline & relapsed HL: PD-1 inhibitors, brentuximab, and sequencing

In terms of how we think about incorporating novel agents into the treatment of the initial treatment of Hodgkin lymphoma, really at this point, we have two regimens, nivolumab AVD, kind of based on an ABVD backbone, and brentuximab vedotin-based regimen, based on an escalated BEACOPP backbone, that are associated with the best outcomes to date in patients with advanced stage Hodgkin lymphoma. And those really are kind of the optimal and recommended regimens. Both regimens actually improved tolerability from their predecessors. So brentuximab vedotin-based regimen is better tolerated than escalated BEACOPP, nivolumab AVD better tolerated than brentuximab vedotin ABVD, and, you know, its predecessor. So, you know, I think in advanced stage Hodgkin lymphoma, for sure, incorporation of novel agents really is a standard. And, you know, if you’re practicing in a location where you have access to these drugs, they really should be incorporated. In terms of early stage disease, I think we are starting to, you know, we have data, smaller phase two studies that have incorporated these novel agents that are associated with excellent outcomes. We don’t have randomized phase three data yet, but we do have some randomized phase two studies. And so there are, you know, these, some of these regimens are now listed in our guidelines. Nivolumab-AVD combined with radiation, rituximab-brentuximab vedotin-AVD combined with radiation, certainly for unfavorable early stage patients. So it’s not quite yet a standard to incorporate novel agents into the frontline treatment of early-stage disease, but there are randomized trials that are ongoing to try to demonstrate that they improve outcomes. Finally, in terms of relapsed disease, it really is a standard at this point to include novel agents in the treatment of relapsed refractory Hodgkin lymphoma. What you use in the second line probably depends a little bit on what was used in the front line. If a brentuximab vedotin-based regimen was used in the front line, unquestionably, a checkpoint blockade and PD-1 blockade should be part of the salvage therapy for second-line treatment of Hodgkin lymphoma. In patients treated with nivolumab AVD, we really don’t have data yet about what the optimal salvage regimen is. Anecdotally, I think we observe that people have used brentuximab-based regimens. We’ve seen many patients actually have been treated with PD-1 blockade, even in patients who had primary refractory disease or early relapse. And I think what we really do need data, at least initially from the real world, but there are some studies that are planned to really assess what the optimal regimen is in patients who have been treated with PD-1 blockade in a frontline setting.

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