ICML 2025 | Guidance for treating patients with double-exposed cHL

This is a really, this is a very relevant question. The double-exposed population in classical Hodgkin lymphoma is a growing population. This is a population of patients who have been exposed to both brentuximab vedotin, an anti-CD30 antibody drug conjugate, as well as a checkpoint inhibitor, anti-PD-1, pembrolizumab or nivolumab. This is a growing population also because these drugs are moving into earlier lines and we’re starting to see both in first-line treatments. So we will be seeing more and more of these patients who have relapsed after being exposed to these drugs and we know they don’t do very well. Their treatment outcomes with whatever treatment they do as a salvage therapy after relapsing, after the second drug, their outcomes are poor and we still haven’t identified exactly what the best approach is for these patients. There’s one of the things that we can do is that we can re-expose them to chemotherapy. Some studies have shown that anti-PD-1 drugs can induce a renewed chemo-sensitization. So although these are generally highly pre-treated patients, they’ve gone through chemotherapy before. Studies have shown that there are results that can be obtained by re-exposing them to chemo. Re-exposure to one of the two drugs that I mentioned either BV or PD-1, some results have been shown in this setting as well especially with anti-PD-1 working with this immuno-modulatory effect and this renewed impact on the tumor microenvironment. And another option that we have that is still utilized in some countries is adopting allogeneic stem cell transplantation. It’s an effective therapeutic approach, but it is also very aggressive therapeutic approach. Non-relapse mortality is still quite high, and these are patients that have gone through prior lines of treatment and exposure to allogeneic stem cell transplantation. It might not even be a possibility for some of them. The eligibility to allotransplant is also a concern. Another option is clinical trials, as always, depending on what is available at different centers in different countries. But the truth is that as of today, we don’t have an answer to the question, what do we do with a patient that is relapsed refractory to both of these novel agents? So we definitely need to study this issue more and hopefully results will be coming out in the following years. And then in terms of the issue of sequencing, the sequentiality of these drugs is also a big question mark. Brentuximab was available before anti-PD-1 drugs. So the historical path that patients have followed is generally to have done brentuximab before anti-PD-1. Now this has been changing. The landscape has evolved and as the drugs have moved through different lines of treatment, we’re seeing that this is no longer necessarily the case. So now the question becomes particularly relevant. So is there perhaps an advantage of doing one drug before the other? And I’m confident that we will be having some results in this aspect as well.

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