Liposomal amphotericin B retrospective multicentre study on mycosis prophylaxis (L-AmB_RUSCO): tolerability and safety of extended-dosing primary antifungal prophylaxis in children with newly diagnosed acute myeloid leukaemia

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OBJECTIVES: To evaluate the tolerability and safety of extended-dosing liposomal amphotericin B (LAmB) as primary antifungal prophylaxis against invasive fungal disease (IFD) in children receiving chemotherapy for newly diagnosed acute myeloid leukaemia (AML); breakthrough proven or probable IFD was assessed as an exploratory secondary endpoint. METHODS: This retrospective, multinational, multicentre observational study included children treated for newly diagnosed AML between January 2019 and December 2023. LAmB was administered according to local protocols at 1 mg/kg three times weekly, 2.5 mg/kg twice weekly or 5 mg/kg once weekly. Clinical and laboratory adverse events (AEs) were assessed to evaluate tolerability and safety. Breakthrough proven or probable IFD, defined according to EORTC/MSG criteria, was recorded as an exploratory secondary outcome. RESULTS: Eighty-six courses of extended-dosing LAmB were analysed. The median age at first LAmB administration was 91 months (IQR 26-156). The median treatment duration was 13 weeks (IQR 3-21) at a median dose of 2.7 mg/kg per infusion, with a median estimated cumulative dose of 77.6 mg/kg (IQR 21.3-110.1). Clinical AEs occurred in 21% of courses, predominantly skin rash and lumbosacral pain. Laboratory AEs were mainly hypokalaemia (48%) and hepatotoxicity (19%), both dose related. Treatment discontinuation due to toxicity occurred in 15% of courses. Breakthrough proven or probable IFD occurred in 3% of cases. CONCLUSIONS: Extended-dosing LAmB represents a reasonably well-tolerated mould-active option for primary antifungal prophylaxis in children with newly diagnosed AML, particularly when triazoles are contraindicated or daily intravenous echinocandin administration is impractical; the low observed rate of breakthrough IFD should be interpreted cautiously given the absence of a comparator group.

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