We have been doing work with an engineered cell therapy, a CAR T-cell therapy, directed against CD19 called CTL019. This is a cell therapy that we’re hoping will be before the Food and Drug Administration very soon for potential approval and in front of EMA pretty soon after that. This cell therapy is very powerful, it’s very good at controlling refractory ALL, but in patients who have very high disease burdens the T-cells have to proliferate to a very high level to kill all the leukaemia. That process produces an enormous amount of inflammatory proteins and cytokines that can make the patient quite ill, indeed there can be ICU level, intensive care unit level, sickness.

So to get to your tocilizumab question, tocilizumab blocks a particular cytokine, a particular inflammatory protein called interleukin-6. It turns out that interleukin-6 is a big part of the toxicity reaction of these very active T-cells. You block IL-6 and the patient can get better very, very quickly. Without tocilizumab we wouldn’t be able to use these cells safely.

In terms of controlling cytokine release syndrome, you could say that tocilizumab always works. In about two-thirds of patients, the paediatric patients on the trials that I’ve been involved with, the tocilizumab will control the cytokine release syndrome very quickly. In the other third of the patients it takes a few days and in those patients they often receive more treatment than just the tocilizumab - they may get steroids for a short period of time, another dose of tocilizumab, and very rarely another cytokine medication; there’s a new medicine now called siltuximab which directly binds to IL-6. So in that third of patients that don’t immediately respond they eventually respond over a few days but require more treatment.

How we sequence these things is a really important question. We have the immunotherapies which are molecular, checkpoint inhibitors which really in the leukaemias is not such an important class of drugs right now, and then, of course, bispecific antibodies like the BiTE blinatumomab and other molecules like that. So those molecules are off the shelf which means a physician can just prescribe them and you don’t have to collect anything from the patient, you don’t have to make a cell therapy. The engineered cell therapies are a step above that, both in terms of efficacy – they’re more efficacious – but also in terms of complexity and cost because you do have to make an individual product for each patient. So you’ll have to balance access against efficacy and it will take a year or two for all of those considerations to sort themselves out. It’s a great question and as we have more and more of these sorts of both cell therapies and molecules available on the market it will be interesting to see how physicians choose to sequence them.

I’m most excited about the fact that we’ve completed a registration trial, that that’s been tested globally, so we’ve done 25 centres in 11 countries including a lot of folks in the EU who participated in these trials in paediatric ALL, that will be in front of the FDA in a very short amount of time and I hope in front of the EMA pretty soon after that.