Glofitamab for Relapsed/Refractory Large B-cell Lymphomas | Joshua Brody, MD | #ASH24

Hi, my name is Josh Brody. I run the lymphoma immunotherapy program at the Icahn School of Medicine at Mount Sinai. So a lot of exciting progress being presented here at the 2024 ASH meeting. Probably if there's an overall theme of exciting things that are impacting our patients today, it is the progress in immunotherapies for patients with all types, especially of B. Selma Hodgkin's lymphomas and particularly some of the most common ones. Diffuse large B-cell lymphoma and follicular lymphoma. For diffuse large B-cell lymphoma, we have had a revolution already in the past few years with FDA approval of a couple of these new immunotherapies by specific antibodies, specifically Glofitimab and Epcoridimab. And here at ASH, we're going to get some follow-up, one of the abstracts about the long-term follow-up of patients who got Glofitimab therapy for their DLBCL after the failure of prior therapies. And the remarkable result here is we have a number of patients who have been in complete remission after Glofitimab monotherapy, just that by itself now for years, some of the longest ones ongoing for three and four years now. So we don't want to oversell this. That first study was about 150 patients. The complete remission rate was just under 40 percent, so significant, but not everybody. But of those patients that got remissions, a remarkable proportion of them, a majority, are still in remission today just from that gentle therapy. And these were patients for whom chemotherapy had failed, many of them for whom CAR T cells had failed, and other therapies. So quite impressive that I would describe as an overall fairly gentle therapy could be so effective and yield these durable remissions. So that's pretty exciting. I have to say probably the most exciting part of it is that this field has not rested on its laurels and is quickly moving that immunotherapy from a Plan C or Plan D, from a third-line therapy to becoming a second and front-line therapy. So now we have a number of ongoing trials of not just the bispecific antibodies by themselves, but combined with standard chemotherapy. And those trials are still ongoing, so we don't have the results yet. But we do have another trial that did complete, well a couple of them actually, of using chemotherapy plus the bispecific antibodies as third-line therapy. One of those is called the STARGLOW trial. Some updates being presented here at ASH, but most of those results were presented a few months ago. The result is incredible. They compared chemotherapy by itself to chemotherapy plus the bispecific antibody, and the result was gigantic. The complete remission rates with chemotherapy plus the bispecific antibody were the majority of patients were getting complete remissions. And overall there was a randomized trial where we saw an overall survival benefit for those folks that got the immunotherapy combined with chemotherapy. So that in some ways I would say could be a new standard of care for third-line therapy, and that is with Glowfidib-Mab plus chemotherapy. We actually have a very similar result from the other bispecific I mentioned, Epcoridumab, but that's a phase two instead of a phase three trial. Nonetheless, the results were extremely similar. The complete remission rates for GEMOX chemotherapy plus Epcoridumab, and we're presenting an update of that here at ASH, were again about 60%. And chemotherapy on its own gives complete remission rates around 30%, depending on the situation and what prior therapies the patient had had. So this is hugely more effective than chemotherapy alone. So a great advance for our patients.