Unexpected Lack of Efficacy of Liposomal-Encapsulated Daunorubicin/Cytarabine in Pediatric FLT3 Wild-Type Newly Diagnosed AML

Contemporary protocols in pediatric AML in higher-income countries reach outcome rates on the order of 60%-70% event-free survival (EFS) and approximately 80% overall survival (OS).1 One of the main concerns in the field is long-term cardiac toxicity related to the cumulative anthracycline dose.2 Studies with liposomal formulations of anthracyclines with reduced uptake in the myocardium have thus been conducted with a goal of mitigating this risk while also preserving antileukemia treatment efficacy. More than a decade ago, Kaspers et al reported that in relapsed pediatric AML, a randomized study of liposomal daunorubicin (DNX) added to a FLAG chemotherapy backbone led to improved early response rates, but not to an OS advantage in the overall group. However, a significant OS benefit was realized for children with core binding factor (CBF) leukemias with DNX-based therapy.3 In another randomized study, Tierens and colleagues4 reported that DNX in induction therapy was less effective compared with mitoxantrone in children with newly diagnosed (ND) AML. DNX is unfortunately no longer available because of its market removal in 2017.