Good morning ladies and gentlemen. I will present the data showing that the diversity of T lymphocytes is extremely important for the fight of the immune system against leukaemia. The full data will be presented on Sunday morning so if you are interested you can also come to the official presentation.

Acute lymphoblastic leukaemia cells carry the CD19 molecule on their surface and the drug which is called blinatumomab uses this CD19 molecule to link leukemic cells to T lymphocytes. Blinatumomab has been recently shown to be highly active in acute lymphoblastic leukaemia and by linking T lymphocytes to acute lymphoblastic cells causes the death of the leukemic cells. T lymphocytes also carry so-called T-cell receptors on their surface and these T-cell receptors are important for recognition of pathogens. The diversity of the receptors is important to recognise the huge variety of pathogens.

So our aim was to assess the diversity of the T-cell receptor repertoire using amplicon next generation sequencing which is the revolutionary modern technology which allows us to assess the diversity with ultra-high resolution and to obtain the DNA sequence from each T-cell receptor gene in the tested sample. Our laboratory in Kiel is a member of the EuroClonality-NGS consortium where this assay is being developed and standardised for use within the whole of Europe and maybe even within the whole world.

So what are our results? We compared the diversity of T-cell receptor repertoire in persisters which are patients not responding to treatment and in responders who respond well to treatment. Here you can see the median diversities at different time points – before therapy, at day 15 of therapy and at day 29 of therapy. We used statistical methods to describe the differences and to decide which differences are significant, which means important, and probably caused by something else than mere chance. As you can see, before therapy the diversity between persisters and responders was very different; the persisters had much lower diversity than the responders. At day 15 there was no significant difference between the two groups and at day 29 again diversity was significantly higher in the responders.

We also looked at the diversity change during treatment and we saw that in responders the increase of diversity between the start of the therapy and day 29 is highly significant whereas in persisters this difference is not significant at all. So we showed that blinatumomab responders have a significantly higher T-cell receptor repertoire diversity already before treatment and that the expansion during blinatumomab treatment is much sharper in responders. Probably further studies on bigger patient cohorts will be necessary to elucidate and to confirm that response to blinatumomab can be predicted by the repertoire diversity before treatment. Thank you for your attention.