I’m talking about CAR T-cells which is a hot topic in ALL therapy. It has been about eight months now that the first product has been approved for use in children and adolescent patients with refractory ALL. There’s still a lot we don’t know about how CAR T-cells act and how we can improve our multimodal therapies implementing CAR T-cell therapy in first or second line therapy rather than just salvaging patients with refractory disease. So I’m reviewing current knowledge on efficacy data, on the potential of CAR T-cells to induce and maintain remissions even without subsequent transplant, to act as a stand-alone therapy potentially and also toxicities associated with the use of CAR T-cells. I’m giving some thoughts and considerations about how to best integrate them with alternative agents into future protocols and how to provide access to all patients who need CAR T-cell therapy to have the best chances of cure.

What are the toxicities associated with CAR T-cell therapy?

As part of the mechanism of action of CAR T-cells patients have high fevers, temperatures, they can have neurotoxicities associated also with this cytokine storm that happens during the first initial expansion of the CAR T-cells in the body. So the mechanisms of toxicity are very much related to the mechanism of action and we will have to find ways to interrupt toxicity while preventing inactivity of the CAR T-cells.

Regarding the future of these therapies, what areas still need research and development?

So far CAR T-cells only work in B-cell malignancies and in B-cell ALL and we have to develop them further to also be effective in T-ALL which is quite difficult because there are no adequate targets in T-ALL. But with some tricks and novel generations of CAR T-cells it may become possible to extend their potential also to T-ALL. So that’s one thing and the other is to still make them more effective to overcome barriers in the body against optimal function and also to prevent CD19 negative relapse by extending the specificity of the CAR T-cells towards other, even B-cell, targets. That’s the main areas of research.