Advancement of Immunotherapy Treatment in Hodgkins Lymphoma

Hi, I'm Dr. Catherine Dieffenbach. I am the director of lymphoma at NYU Promotor Cancer Center, and I would love to talk to you about what I have presented at the ASH 2023 conference on Hodgkin Lymphoma. So, first as background, Hodgkin Lymphoma is generally a disease of the young, but there's a second peak for older adults who generally don't have as good an outcome as younger patients. Hodgkin Lymphoma has been one of our success stories, and we cure many patients with first line chemotherapy, but for patients who relapse after chemotherapy, it becomes much harder to cure them. At this meeting, I presented a randomized phase two clinical trial of the combination of the antibody drug conjugate, brantuximabidotin, which targets CD30 on the surface of the Hodgkin cell, something that is a protein that's expressed on the surface of the Hodgkin cell, but very few other cells, which makes it a very good target, and one or two immune checkpoint inhibitors. These are drugs that wake up the immune system, and the two drugs that I used were nivolumab and ipilimumab. So, this study started as sequential phase one studies combining brantuximab, the antibody drug conjugate, with ipilimumab or nivolumab, or both together, and this actually introduced immunotherapy into the Hodgkin lymphoma space. The study I presented today was taking the most promising two arms, the doublet of brantuximab and nivolumab, and the triplet of brantuximab, ipilimumab, and nivolumab, and randomizing 120 patients with relapse Hodgkin lymphoma between these two arms. In terms of safety, we saw that both arms were quite safe, with a significant increase in grade three rash, so moderately bad rash, in patients who got the triplet as opposed to the doublet, but this rash could be treated with steroid creams or, if needed, topical steroids. Otherwise, both regimens were safe and pretty well balanced. We saw a non-significant difference of approximately 6% in favor of the triplet arm compared to the doublet, but this did not meet statistical significance, and this was the primary endpoint of the study. When we looked at the progression-free survival and duration of response in the responders, for the duration of response at 24 months, we saw a 9% improvement in progression-free survival for the triplet versus the doublet, which is not yet significant, but may well be with further time to follow these curves. We'll be following patients for five years for progression-free and overall survival. We also looked at the impact of stem cell transplantation on patients who received this therapy, and for patients who went to transplant, who went to autologous stem cell transplant, after this, the responses were tremendous. So, in general, with a chemotherapy to get you into a second remission before transplant, transplant generally results in cure in about 50 to 60% of patients. We saw in our patients in either arm who went to transplant a 24-month disease-free survival of greater than 87%, which is enormously exciting, basically suggesting that for patients who had not received a checkpoint inhibitor therapy, if they received antibody drug conjugate with checkpoint or probably chemotherapy with checkpoint, their outcome from transplant is going to be substantially and significantly better than if they receive only chemotherapy before their transplant. We also looked at the impact of this therapy on patients who elected not to go to transplant, and only 13% of the patients who allotted not to go to transplant had actually had a transplant, so most of these were just patients who didn't want to go to transplant. And what we saw was an 11% improvement at 24 months for the triplet of Brentuximab, Nivalimab, and Ipilimab over the doublet. This 11% difference was trending towards significance, but has not yet reached significance. However, if the trend continues, should reach significance the next time we cut the data. So, that was the abstract that we presented, and you can reach out to me anytime with questions. Thank you.