ICML 2025 | A large retrospective analysis evaluating changes in transplant outcomes over time in relapsed HL

Good morning, good afternoon, good evening. So I’m presenting this study on behalf of the EBMT Lymphoma Working Party, and actually I presented it at the last ICML meeting in Lugano a few days ago. So as you know, autologous stem cell transplant remains a standard of care for patients with chemosensitive relapsed/refractory Hodgkin lymphoma and allogeneic transplant for patients who failed a prior autotransplant. And when we look to the EBMT recommendations for transplant published in 2019, 2022, and very soon for 2025, these indications have not changed. However, what has changed is that over time is that we have new treatment, mostly brentuximab vedotin, and checkpoint inhibitors that have changed the landscape of Hodgkin lymphoma treatment from first line to relapse. 

So the aim of this EBMT study was to assess changes over time in patient characteristics and post-transplant outcome for transplanted Hodgkin lymphoma using the very large data set from the EBMT registry. So the inclusion criteria were adults with classical Hodgkin lymphoma who received a first autotransplant or allo between 2010 and 2022. 

So starting with autotransplant, when we look to baseline characteristics over time, we can see that in recent periods, patients are older with a median age of 36 for 2019-2022 compared to 34 for 2010-2015. And they are more frequently transplanted in complete remission, 70% versus 47%, less frequently PET positive at transplant, 30% instead of 60% before, and they are more frequently receiving mostly brentuximab vedotin before autotransplant in around 20% to 25% of patients and to a lesser extent checkpoint inhibitor. 

So when we look to the outcome over time, we can see that progression-free survival has increased significantly from 63% to 73% at two years, and this is mostly due to decreased incidence of relapse. However, this improvement outcome is not related to improvement in transplant technique because when we look to patients in complete remission at transplant, their outcome has not changed over time. So the improvement that we are seeing in autotransplant is mostly due to the fact that because of these new medications such as brentuximab vedotin, and checkpoint inhibitors used before transplant, we are able to bring patients to transplant in complete remission, and therefore the outcome has improved. 

And when we look to multivariate analysis, to factors affecting the outcome after auto-transplant, the year of transplant is very important, so improved overall survival and progression-free survival over time. The age is important for overall survival. Disease status at transplant is critical for progression-free and overall survival with the best results in complete remission, then partial response, then relapsed/refractory status. And finally, patient receiving BEAM conditioning did better compared to those that received other conditioning. 

So now moving to allotransplant… So I forgot to mention that this study included around 20,000 patients who received a transplant for Hodgkin lymphoma, around 16,000 auto-transplant and 4,000 allotransplant. So now about the 4,000 allotransplants, again, when we look to patient characteristics, so over time, we are transplanting less frequently patients in relapsed or progressive disease or active disease at transplant. So decreasing from 30% to 14%. PET positivity before allo decreased from 60% to 40%. And we are allografting patients mostly after having received brentuximab vedotin, or checkpoint inhibitor. Only one-third of allotransplant in recent period did not receive brentuximab vedotin, or checkpoint inhibitor before allo. One-third received BV only, and one-third received both. 

And in terms of transplant technique, over time we are using more and more haploidentical transplant as modality for donor selection. And the majority of patients in the recent period have received post-transplant cyclophosphamide for GvHD prophylaxis. So when we look to the outcomes, here also we have a major increase in progression-free survival and overall survival. So PFS increased from 44% to 62%. And this is mostly due to decreased incidence of relapse, which decreased from 40% to 18%, so more than half of the incidence of relapse, whereas non-relapse mortality did not change. And this time for allotransplant, contrary to autotransplant, the improvement is not only due to the fact that we are transplanting more patients in complete remission, but also a genuine improvement in transplant techniques, because overall, if we take, for example, patients in complete remission, we have a significant increase in progression-free survival over time for these patients and decrease in relapse incidence. So in trying to understand why, we did a subgroup analysis for patients who received checkpoint inhibitor versus those who did not. And we can see that checkpoint inhibitor before allo results in decreased incidence of relapse, improved progression-free survival and GvHD relapse-free survival, or GRFS. And similarly, the use of post-transplant cyclophosphamide for GvHD prophylaxis improved PFS and GRFS, mostly due to decreased incidence of relapse. 

So in multivariate analysis for allotransplant, here again, the year of transplant, the age of the patient, and the disease status at transplant are major determinants for progression-free survival and overall survival. Conditioning regimen, myeloablative conditioning negatively affects overall survival through increased mortality, and match-related donor, match-sibling donor are associated with the best overall survival. 

So if we want to summarize this study, this is a very large contemporary cohort of patients transplanted for classical Hodgkin lymphoma, including around 20,000 patients. This is by far, I think, the largest in that setting. We have seen that transplanted patients are older and more frequently in complete remission and PET negative at transplant, and we have seen continuously improving progression-free survival and overall survival after auto and allotransplant. After autotransplant, mostly due to the fact that we are bringing patients in complete remission to transplant after allotransplant, both the fact that we are bringing patients in CR but also improvement in transplant techniques. So, brentuximab vedotin, and checkpoint inhibitors are increasingly used before auto and allo, and pre-allo use of checkpoint inhibitor and post-transplant cyclophosphamide improve outcomes in univariate analysis. So in auto-transplant, age and disease status are the major determinant for PFS and OS. In allotransplant, age and disease status are again major determinants, but match-related donor and reduced intensity conditioning yield the best outcome. And thank you for your attention.

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