• chronic myeloid leukemia
• drug plasma concentration monitoring
• ponatinib
• tyrosine kinase inhibitors

Tyrosine Kinase Inhibitors (TKIs) treatment deeply changed Chronic Myeloid Leukemia (CML) natural history with a favorable long-term outcome in more than 90% of patients. Among those drugs, 3rd generation TKI Ponatinib allowed to obtain satisfying responses in patients who failed multiple therapeutic approaches or in case of multi-resistant T315I point-mutation.
Nevertheless, TKIs - especially Ponatinib - are burdened by long-term multi-systemic toxicities as well as by an increased risk of cardiovascular events; those side effects are frequently dose-dependant and in recent years many studies tried to develop guidelines for TKIs dose-reduction to find a new balance between efficacy and toxicity.
In our research, we tested TKIs concentration in CML patients’ plasma samples to analyze both intra- and inter-subject variability; pharmacological findings has been then correlated to clinical data - CML response and side effects - to develop a new tool helping physicians in choices regarding TKIs switch or dose modifications.