Antifungal prophylaxis in patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia receiving sorafenib during initial induction and consolidation treatment in ALLG AMLM16 trial.

Objectives: To report the rates of proven, probable and possible invasive fungal disease (IFD) in patients receiving antifungal prophylaxis during initial induction and consolidation treatment of acute myeloid leukaemia (AML) plus either sorafenib or placebo.

Methods: As part of a randomized, double-blind trial of sorafenib or placebo in combination with intensive chemotherapy for newly diagnosed adult patients with FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)-positive AML (ALLG AMLM16 trial), liposomal amphotericin B (LAMB) prophylaxis was administered at 5 mg/kg twice weekly during induction and consolidation phases in both sorafenib and placebo treatment arms. Alternative prophylaxis was allowed per institutional practice once sorafenib/placebo treatment was completed. IFD episodes, reported as either a serious adverse event or an adverse event, were adjudicated.

Results: Of the 94 patients included for analysis of IFD, four IFD episodes (one proven and three possible) were reported during the induction treatment phase. The overall rate of proven/probable/possible IFD was 4.3% (4/94), with rates of 3.1% (2/64) and 6.7% (2/30) in the sorafenib and placebo groups, respectively. Seven patients had infusion-related reactions, and four were reported to be associated with LAMB administration.

Conclusions: LAMB with or without subsequent azole prophylaxis could be an alternative option for fungal prophylaxis for patients with AML in whom azoles are contraindicated or not tolerated. Sorafenib does not appear to be associated with an increased risk of IFD.