A New Precision Medicine Approach for Curing Chronic Myeloid Leukaemia: translation to clinical practice

With current therapeutical approaches, around only 30% of all CML patients can achieve Treatment-Free Remission (TFR), the ultimate goal of CML therapy, and maintain this long-term. The remaining 70% are dependent on lifelong therapy with Tyrosine Kinase Inhibitors (TKIs) to maintain control of the disease. We have recently discovered two key barriers to TFR and developed novel biomarkers to assess these barriers:    Barrier 1 – Residual leukaemia in critical cell compartments: We have shown that leukaemia detection in granulocytes at the time of stopping TKI treatment is highly predictive of TFR-failure.    Barrier 2- Impaired immune mediated leukaemia control: Decreased immune suppressors (myeloid-derived suppressor cells and regulatory T cells) and increased immune effectors (NK cells) strongly predict TFR success. We have developed an effector/suppressor score to quantify this immune-mediated control.    Hypothesis: Determining how these biomarkers change over time and how they interact will lead to new pathways to cure for CML patients.

This project will develop widely applicable predictive tests of TFR outcome that can be introduced in clinical setting, and facilitate the rational design of interventional clinical trials aiming to improve TFR achievement. Moreover, we will gain much greater insight into the dynamics of leukaemia eradication and immune control in different CML settings which will lead to new therapeutics opportunities, and partnerships with pharmaceutical companies. This new understanding will allow us to develop a precision medicine approach specific for every CML patient and to translate it to clinical practice over the next five years.