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.

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.