Dynamic modelling of the immune response in patients with TKI-treated CML

General background: The use of thyrosine kinase inhibitors (TKIs) is a very effective therapy for the treatment of chronic myeloid leukaemia (CML). Although TKI therapy can control the disease for the majority of patients and the probability of survival is almost the same as that observed in an age-matched population of healthy people, it has not yet been shown that treatment with TKIs actually leads to a cure. Lifelong TKI treatment is still the default.

Specific motivation: A number of studies and basic medical experiments suggest that the immune system plays a central role in the success of therapy. In particular, the question of the extent to which the individual immune response is responsible for the fact that some patients remain permanently in remission after discontinuation of TKI treatment (i.e. no or only very little evidence of leukaemic cells), whereas in other patients there is a renewed increase in the tumour burden (i.e. the proportion of leukaemic cells) and TKI therapy must be continued.

Results: In this project, we are modelling the interaction of TKI treatment with immune system effects to gain a better understanding of the influence of the immune response on therapy success. The use of ordinary differential equation models (ODE models) shows, among other things, that it is possible to categorise patients into different classes according to the effectiveness of their specific immune response. In the future, this grouping may help to better tailor therapy to the individual circumstances of patients. Our results also indicate that different therapeutic strategies are possible on the way to a complete stop of TKI treatment. Our modelling shows possibilities for reducing the frequency of side effects and the costs of therapy without losing effectiveness.