What we’re here talking about at the ASH meeting is an update to the ELIANA trial. That’s a registration trial of CAR T for children and young adults with ALL. It was the first registration trial in CAR T; it was the first global trial, global logistics, first supplied by drug company supply, so there are a lot of firsts. This is actually an update so we’ve already presented that information, it was used for the FDA and then the EMA approvals of Kymriah, but now we have longer term follow-up data and that’s actually what’s most interesting.
What’s new, so we’re seeing exactly the same short-term characteristics – 82% of the patients going into remission, the same safety profile across 25 centres in eleven countries, so that all looks quite good. We’re clearly able to do this safely and at scale. But what we didn’t know is once you go into remission how long does it last and that’s super-important, that’s really what the patients are looking for. So what we’re seeing with that is that at 12 months, at 18 months, two-thirds of the patients are still in remission if they entered a remission and that’s a really key time point for us. At two years it’s 62%, or very similar, and so that shows that there is a group of patients who can stay in long-term remission and most of those patients didn’t get any further therapy such as stem cell transplant. So this clearly starts to indicate to us that there’s a group that can actually use CAR T, specifically Kymriah, as definitive therapy for ALL.
What’s your take-home message for doctors?
The take-home message really is that when patients enter remission after CAR T, at least using this Kymriah product, that two-thirds of them stay in remission at 18 months. So that seems to say to us that there are patients who are going to have long-term disease control just with the CAR T product.
The second bit of data is particularly interesting and this is new. We had treated these patients, we evaluated their response at day 28 and we did the standard test for minimal residual disease to see that they had deep remissions which is multi-parameter flow, which in the United States is the standard test, in Europe it’s allele specific PCR, the performance of the two tests is very similar. The good news is everybody was MRD negative, or everybody but one person was MRD negative, the bad news is that doesn’t allow you to discriminate anything because everybody is negative. So they resubmitted those samples for a different test and this is MRD by next generation sequencing, or high throughput sequencing, and where they’re actually sequencing the antigen receptor gene rearrangements in each cell. That’s much more sensitive, at least a log and probably more than a log more sensitive. Now we’re starting to see patients who are positive and negative by that test, most negative but some positive. What’s the result of that? If you’re negative by that more sensitive test there’s an 80% likelihood that you’ll stay in remission; if you’re positive by that more powerful test, that more sensitive test, there’s a 20% chance that you’ll stay in remission. For that positive group that says maybe we need to consider more therapy, maybe transplant is actually the right thing to do for those patients, we have to think about that. For the negative group, 80% likelihood of staying in remission, that is a powerful indication to me that those patients don’t need a transplant.