A retrospective analysis of newly diagnosed acute myeloid leukaemia patients receiving venetoclax and a hypomethylating (Ven/HMA) agent finds that azole antifungal prophylaxis (AFP) did not improve the overall survival of participants. Patients who received azole antifungal prophylaxis had an inferior overall survival, with 34% of patients receiving AFP having died by day 120 compared to 25% of those not receiving AFP. Regardless of the azole antifungal agent used, a similar lack of benefit was observed: voriconazole (HR=1.04, p=0.75), fluconazole (HR=1.26, p=0.039), isavuconazole (HR=1.52, p=0.048), and posaconazole (HR=1.62, p=0.005).
Venetoclax is now standard care for older adults with AML or those with comorbidities unfit for intensive chemotherapy. It prolongs survival time: ~14.7 months compared to ~9.6 months with azacitidine alone.
The findings from this study by Ambinder and colleagues from the USA contrast with the previously known proven benefits of AFP with mould-active azoles in patients receiving intensive chemotherapy. The explanation may lie with a lower fungal infection risk or the challenge of inadequate venetoclax dose reductions following drug-drug interactions. In addition, the use of antifungal prophylaxis was associated with higher rates of prolonged neutropenia. The authors recommend administering azoles after the completion of the venetoclax dosing period in patients experiencing prolonged neutropenia to provide antifungal coverage while avoiding drug-drug interactions during the period of maximal venetoclax exposure.
