NEW TARGETED DRUGS FOR ACUTE MYELOID LEUKEMIA AND ANTIFUNGALS: PHARMACOKINETIC CHALLENGES AND OPPORTUNITIES

: Background Acute myeloid leukemia (AML) is a life-threatening disease whose treatment is made difficult by a number of mutations or receptor overexpression in the proliferating cellular clones. Life expectancy of patients diagnosed with new, relapsed-refractory or secondary AML has been improved by drugs targeted at such moieties. Regrettably, however, clinical use of new AML drugs is complicated by pharmacokinetic interactions with other drugs the patient is exposed to. Summary The most relevant drug-drug interactions (DDI) with clinical implications build on competition for or induction/inhibition of CYP3A4, which is a versatile metabolizer of a plethora of pharmacological agents. Here we review DDI between AML drugs and the agents used to prevent or treat invasive fungal infections (IFI). The pathophysiology of AML, characterized by functionally defective white blood cells and neutropenic/immunosoppressive effects of concomitant induction chemotherapy, can in fact increase the risk of infectious complications, with IFI causing high rates of morbidity and mortality. Triazole antifungals, such as posaconazole, are strong inhibitors of CYP3A4 and may thus cause patient's overexposure to AML drugs that are metabolized by CYP3A4. We describe potential strategies to minimize the consequences of DDI between triazole antifungals and targeted therapies for acute myeloid leukemia and the role that collaboration between clinical pharmacologists, hematologists and clinical or laboratory microbiologists may have in these settings. Key Messages Therapeutic drug monitoring and clinical pharmacology stewardship could represent two strategies that best express multidisciplinary collaboration for improving patient management.