Section: Research Program

Leukemia modeling

Imatinib and other tyrosine kinase inhibitors (TKIs) have marked a revolution in the treatment of Chronic Myelogenous Leukemia (CML). Yet, most patients are not cured, and must take their treatment for life. Deeper mechanistic understanding could improve TKI combination therapies to better control the residual leukemic cell population. In a collaboration with the Hospital Lyon Sud and the University of Maryland, we have developed mathematical models that integrate CML and an autologous immune response ([11], [12] and [34]). These studies have lent theoretical support to the idea that the immune system plays a rôle in maintaining remission over long periods. Our mathematical model predicts that upon treatment discontinuation, the immune system can control the disease and prevent a relapse. There is however a possibility for relapse via a sneak-though mechanism [11]. Research in the next four years will focus in the Phase III PETALS trial. In the PETALS trial (https://clinicaltrials.gov/ct2/show/NCT02201459), the second generation TKI Nilotinib is combined with Peg-IFN, an interferon that is thought to enhance the immune response. We plan to: 1) Adapt the model to take into account the early dynamics (first three months). 2) Use a mixed-effect approach to analyse the effect of the combination, and find population and individual parameters related to treatment efficacy and immune system response. 3) Optimise long-term treatment strategies to reduce or cease treatment and make personalised predictions based on mixed-effect parameters, to minimise the long-term probability of relapse.