VIDEO: Research updates in DLBCL

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Actually, there were a huge number of, I would say, clinically meaningful updates at ASH 2022. Perhaps one of the most directly impactful was a large trial done in Europe looking at primary CNS lymphoma, which we sometimes think about as a subset of DLBCL. And in frontline therapy for primary CNS lymphoma, we're lucky to have some regimens, multi methotrexate-based regimens that induce remissions. But in terms of long term durable remissions, there's a great unmet need there. And also certainly in terms of being able to accomplish durable remissions, hopefully with avoiding whole brain radiotherapy, which can have real toxicity.

So, a large randomized trial, basically comparing the inclusion of upfront consolidation with autologous stem cell transplant. As we talked about, in second line DLCBL transplant is actually getting less space as CAR Ts are perhaps taking over. But in this large randomized trial, there was a marked survival benefit, the gold standard of all clinical research, in overall survival benefit for patients getting a matrix chemotherapy, somewhat more complex regimen than just plain old methotrexate by itself. And so this trial was focused on the younger patients, which are still a significant proportion of our primary CNS lymphomas. And then following up that matrix induction chemotherapy with autologous stem cell transplant, large progression-free survival, large overall survival benefit. And again, this is not gentle therapy. But brain lymphoma can be a quite aggressive disease. So sometimes we need aggressive therapies to get great long-term outcomes. So that was a huge impact from ASH 2022.

I would say amongst the many other impactful presentations, an overall theme was the increasing utility of bispecific antibodies. These are mostly CD3 by CD20 bispecific antibodies, not in any order, but mosunetuzimab, glofitimab, epcoritimab, three of the furthest along. And here now, we just have the recent FDA approval of mosunetuzimab for follicular lymphoma, and we'll probably have FDA approvals of epcoritimab and glofitimab for DLBCL third line therapies later this year. And just more and more presentations about the role of these bispecifics in third line DLBCL in combinations of chemotherapy plus bispecific antibodies with very high efficacy and pretty good tolerability. And in some ways, these are going to become direct or indirect competitors with CAR T-cells, because probably won't have a head-to-head trial. But certainly, when you look at chemotherapy plus bispecifics, the efficacy numbers and the data's a bit earlier than the CAR T-cell data, so we don't know if these remissions will last for years, like many of the CAR T patients. But the efficacy data has been so awesome with bispecific antibodies plus chemotherapy, and even bispecific antibodies by themselves, that these may become a standard third line therapy for perhaps majority of DLBCL patients. But as I mentioned, I think that these bispecific antibodies will quickly, and the trials have already started, worked their way up into even frontline therapy. So yeah, just a lot more data about that at ASH about long term follow up from some of these patients doing incredibly well with durable remissions.