ASH 2024 | Low-dose radiation as bridging to CAR-T therapy in patients with aggressive B-cell lymphomas

The optimal bridging therapy remains undetermined in sequencing and thinking about therapies prior to CAR T-cell therapy for relapsed/refractory aggressive B-cell lymphomas, including diffuse large B-cell lymphoma. Optimally, your bridging therapy should be able to achieve several tasks. One, it should keep your patient in good shape so that they’re not damaged by the side effects of the toxicity of the bridging therapy and weakening their ability to make it through CAR T-cell therapy. Two, it should provide some semblance of disease control, at least trying to keep the lid on the disease coming into CAR T-cell therapy. And then optimally, in the best case scenario, it would actually help make the CAR T-cell therapies even more effective, as ultimately that’s going to be the most important therapy in achieving the best outcomes for our patients that are receiving CAR T-cells. So we conceived with the Boom Boom study, which is Boom Boom radiation is two gray given in two doses. So it’s a very easy and very feasible type of radiation. It is administered on a simple schedule over two days and very easy for remote patients that are trying to access CAR-T sites from far away. It’s not a complicated dosing schedule or anything like that. And there’s preclinical data in the mouse models of CAR T-cells that this low dose is actually kind of the Goldilocks in some kind of way as it comes to radiation therapy. If you use too high a dose, you might not actually achieve the optimal CAR-T kind of an immune enhancement that can come along with radiation. And this low dose administered as close as you can to CAR T-cell therapy might prove even more immune stimulatory. It might actually make the whole CAR T-cell therapy and the whole care that comes along with it, not just the cells themselves, but the rest of your immune system and everything, all work better. And so that was the rationale for doing this study. And what we’re reporting here at ASH this year is an interim analysis on the first 20 subjects that have been recruited. We are near completing the recruitment of our study. But in the first 20 patients that we’re seeing, what surprised us was the amount of efficacy after CAR-T. Despite enrolling a pretty high-risk population, 65% of patients had extranodal disease presentations, 70% had elevated LDH at the time of study entry, and the majority of patients had advanced stage disease. Despite these aggressive characteristics and higher risk characteristics, we saw over 80% CR rates. In fact, any one of our patients that were responding were in complete response and did not have any partial responses. This is really important because the depth of response matters in looking at the efficacy of CAR T-cell therapy. And if we can demonstrate some evidence that we’re producing higher rates of CRs, it’s certainly encouraging and worthy of further exploration, in particular if we’re able to continue to see how our study reads out. So we were excited to share that data. In fact, it was simple to deliver as well, so we have a feasible strategy and easy-to-deliver therapy and something that could pair well with additional bridging strategies if we needed additional debulking or something. So exciting to see how this study will continue to mature.

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