CAR-T Meeting 2025 | A “dose-dense” approach to CAR-T administration in a trial investigating JCAR014 in B-cell lymphoma

So this novel trial that explores this dose-dense approach is about patients with aggressive B-cell lymphomas that receive CAR T-cell therapy. So in this particular trial there was a particular cohort where patients would receive JCAR014 at a conventional dose of 2 million cells per kilogram on day zero after lympho-depleting chemotherapy. So in this particular cohort patients will receive a second 2 million CAR T-cells per kilogram dose very early on, on day 14. So in the second week after the first infusion we will receive a second infusion. 

So the idea behind this cohort is to see if by increasing the total cell dose infused you could potentially increase efficacy or the quality of the response. But also the idea of increasing cell dose raises the issue of if this is going to be safe. You know the higher the dose that you give, also the higher the likelihood that you will have severe CRS, severe ICANS. So the other idea is if you delay the second infusion you might be able to give a higher dose without compromising safety. 

So in this trial there were 17 patients that were able to receive these two doses. So one of the most important findings in this trial is that almost saw all CRS and ICANS or neurotoxicity events were observed after the first infusion. So after these events cooled off and patients received the second infusion it was very rare to see a new onset of CRS or ICANS. In fact, only one patient developed a very mild and transient  CRS that was resolved spontaneously. So we know that it was safe. It doesn’t significantly increase toxicity at all, almost, and doesn’t increase all-cause mortality. So we know that it seems to be safe. 

Regarding efficacy, what we saw is that in comparison to another cohort in the same clinical trial where patients with aggressive B-cell lymphomas received only standard one dose of 2 million cells per kilogram, if you try to compare the outcomes of this dose-dense approach, you could see that the likelihood of achieving a response was almost comparable, almost the same, but the difference was on the duration of response. So we almost saw how the median duration of response almost was quadrupled, multiplied by 4, in patients receiving this dose-dense approach. 

So this could be a really important thing because if this is confirmed, then it could mean that with the same resources that we have today, if we apply this more broadly, could potentially increase significantly the quality of response of patients to CAR-T therapy with the same resources, so you could potentially increase the cost-benefit of these treatments.

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