My talk will be essentially about the post-transplant interventions to both prevent and treat relapse. It will focus on the use of donor lymphocyte infusions, a bit about tyrosine kinase inhibitors. I’ll touch on CAR T-cells, and of course, mention second transplant.
To look at them in more detail. If you have a person who’s about to relapse, you have early evidence of relapse at say the molecular level, the first thing you would do is withdraw their immune suppression in the hope of enhancing a graft versus leukemia effect...
My talk will be essentially about the post-transplant interventions to both prevent and treat relapse. It will focus on the use of donor lymphocyte infusions, a bit about tyrosine kinase inhibitors. I’ll touch on CAR T-cells, and of course, mention second transplant.
To look at them in more detail. If you have a person who’s about to relapse, you have early evidence of relapse at say the molecular level, the first thing you would do is withdraw their immune suppression in the hope of enhancing a graft versus leukemia effect. The overall evidence is that this is not an effective strategy. You may get graft versus host disease. You may get some response in the ALL, but it doesn’t result in durable control.
The next strategy worth considering is giving donor lymphocyte infusions. And we have a bit of data from, that from our recently concluded trial, UKALL14. We did about 250 reduced intensity transplants and for the patients who had molecular relapse, we gave them donor lymphocyte infusions. And what we found out in moderate numbers of patients is that about half of them responded. But again, it was disappointing in terms of long-term control. We had very few long-term survivors. And this is not really new, we’ve never really felt that donor lymphocyte infusions produced durable control.
The therapy of choice for post-allograft relapse is CAR T-cells. So if you’re under the age of 26, we have a licensed product, tisagenlecleucel that can produce good survival at two years, around 50% disease-free survival. That, unfortunately, leaves people over the age of 26, who do not have a licensed product. There’s a number of trials, there are trials of Autolus, of Kite, of Celgene. And hopefully, those trials will result in CAR T-cells coming to the market for that group. There’s some data from the University of Pennsylvania showing efficacy, and there was also more toxicity necessitating fractionating the dose.
Another thing to mention is of Philadelphia positive disease using tyrosine kinase inhibitors. And they can be very effective therapy. If you institute a TKI at the point of molecular relapse, or of course, given prophylactically, these are both effective therapies and there was a German group study showing that.
I think the other thing to mention is second transplants. So this is not something that our group have done very much of, because we don’t really see good evidence for it. Some people are doing it now. They will use targeted therapies post-transplant and try and get the person back into molecular remission, then do a second transplant. But there really is a paucity of data showing that you can do this and cure patients. In particular, the GIMEMA group, they haven’t published these data, but in quite large numbers of patients, they have less than 5% survival. However, with the advent of targeted therapies, it’s certainly something to consider.