EBMT 2021 | MABs for Hodgkin lymphoma

Thank you, good morning, good afternoon, good evening, everybody. I would like to thank you for the kind invitation. So basically, I will be summarizing my presentation at the EBMT meeting on monoclonal antibodies and Hodgkin lymphoma.

So, as you know, Hodgkin lymphoma is a unique disease and that relapses can be salvaged having to cure in more than 50%, and the standard of care for a patient with Hodgkin lymphoma failing first-line therapy is salvage chemotherapy, followed by autologous stem cell transplant. And basically, different combination chemotherapy were tested in term of salvage that they are quite comparable with around 30% complete remission rate and 70% overall response rate. And it is better to be in complete remission before transplant.

And actually, as you know, we have monoclonal antibodies that have recently changed the landscape of Hodgkin lymphoma. These are brentuximab vedotin targeting CD30, so it’s an anti-CD30 monoclonal combined with, carrying a chemotherapy product, and we have checkpoint inhibitors, particularly nivolumab and pembrolizumab, that are quite efficacious.

To summarize my talk, basically, these new drug combination-based salvage therapy before auto-transplant have tremendously increased the rate of response and complete remission. So basically, when you combine brentuximab vedotin, for example with chemotherapy in patients failing first-line treatment, you have around 90% response rate, 70% metabolic CR. So, it’s more than doubling the rate of complete remission before transplant with outstanding PFS post-transplant.

Also, these monoclonal antibodies can be used in addition to a salvage pre-transplant. They can be used as consolidation after auto-transplant to prevent relapse and we have both the AETHERA study for brentuximab vedotin, and a new Phase II studies for checkpoint inhibitors alone or combined with BV that are quite promising.

However, not all patients do well after auto-transplant. So, those who relapse after auto can respond to brentuximab vedotin, can respond to checkpoint inhibitors, however, a few of them will be cured without allo-transplants, so allogenic transplant remains a potentially curative strategy for patients who fail auto-transplant. However, monoclonal antibodies are quite useful as bridge to allo, allowing patients who relapse after auto to respond again so that they are able to undergo allogeneic transplant.

Both brentuximab vedotin and checkpoint inhibitors can be safely used before allo-transplant or even for relapse after allo-transplant. However, we should be cautious when using checkpoint inhibitors. We need at least two months before allo and at least six months after allo as a window where we should not be using checkpoint inhibitors to avoid severe graft-versus-host disease.

So currently, with these results, the overall survival after, for a patient relapsing after auto has significantly increased in recent years and this is a presentation that we made at the last ASH meeting. And four-year survival increased from 30% for patient who relapsed 20 years ago, to above 60% for patients who relapsed in the recent years. This is a great hope for Hodgkin lymphoma patients.