EHA 2025 | The use of BOOM-BOOM radiation prior to liso-cel in aggressive B-cell non-Hodgkin lymphoma

BOOM-BOOM radiation, which is a really low dose of radiation, is given as a total of four gray, two gray, in two fractions. And our hypothesis in designing this study was that BOOM-BOOM radiation would be very safe and easy to deliver as a bridging therapy prior to CAR-T and also might help improve the CAR-T response by some immunologic mechanisms that kind of allow the innate immune system to better get into the tumor microenvironment, might recruit other parts of the immune system, it might allow CAR T-cells to get better access into the tumor microenvironment. 

So our primary endpoint of the study was feasibility. We just wanted to make sure first that this could actually be done for our patients. One of the unique things about our medical center in Omaha, Nebraska is that we recruit from a large territory and so most of our patients are rural and drive many hours to come in. So that feasibility was very important to us. We saw in our 32 patient study, 30 of those patients that were enrolled went on to receive BOOM-BOOM and CAR T-cell therapy, hitting our key feasibility threshold. 

So then when we took a look at efficacy, sorry to backtrack just a little bit, the BOOM-BOOM radiation was given about a week before CAR-T infusion and sort of in just enough time to kind of be in effective bridging therapy but also be given near the CAR-T time so that it could help augment the product’s efficacy. 

So when we delivered that therapy, we saw encouraging response rates. Our CR rate for the cohort of about in the evaluable patients, which was 29 patients of the 30 that received the treatment, we saw a CR rate of 86 percent. And that’s encouraging because it’s certainly higher than what was reported for the registrational trials for liso-cel, and this was a study that all patients received liso-cel as their CAR-T therapy. So it was very encouraging to see there. We also saw some early signs of durability. Our median follow-up is 140 days, but we are seeing good progression-free survival and good overall survival too. 60% or so are alive and progression-free so far on the study. And by using a landmark analysis and looking at those people that made it to their day 30 response and then separating by responses, we see very encouraging progression-free survival data where 75% or so at 200 days remain alive and progression-free. 

So these numbers are very exciting for us, especially given the toxicity profile of BOOM-BOOM radiation, which is very low. It looks very easy to deliver, only given over two fractions, and no new signs of cytopenias or infections that came from this. The CRS rate was similar to what was expected and compared to in the other trials. The ICANS rate was a little bit higher than expected in this study cohort and I suspect that has more to do with the patient population that we recruited. Our median age was 70 years on this study that’s older than what was reported in the TRANSCEND and TRANSFORM trials for liso-cel and that tends to be one of the factors that factors in on ICANS toxicity, that’s certainly where we saw more of our ICANS toxicity was in our older patients too. So I don’t think it was a radiation effect though of course we certainly need to do a little bit more data gathering to understand that for sure. 

So we’re very excited about this data and we think that BOOM-BOOM radiation could really be an opportunity to enhance the efficacy of the CAR-T product with a very low cost low toxicity approach.

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