Blood cancers

Experts back antifungal prophylaxis alongside novel AML therapies

International experts have broadly backed antifungal prophylaxis in patients taking novel targeted therapies for acute myeloid leukaemia (AML), having taken a renewed look at the strategy in light of new and diversifying treatments for the condition.

The research team – comprised of experts in infectious diseases, haematology, oncology, clinical pharmacology and methodology – was commissioned by the European Haematology Association to assess potential drug-drug interactions and the resulting risk-benefit ratio for preventing invasive fungal disease in patients taking newer antileukaemic medicines, and thus tighten up clinical practice in the area.

The guidance, published in The Lancet Haematology, recommends antifungal prophylaxis with moderate strength in most clinical settings involving novel targeted agents, but with a strong recommendation when the novel AML therapy is given alongside intensive induction chemotherapy.

Based on low-certainty evidence, standard use of antifungal prophylaxis was not recommended for patients with AML treated with azacitidine or decitabine monotherapy, but can be considered in those at greater risk of invasive fungal disease, such as patients with neutropenia at treatment onset of those who have previously received intensive chemotherapy.

Antifungal prophylaxis – preferably with a triazole – is also recommended for AML patients taking venetoclax in combination with a hypomethylating agent and at high risk of invasive fungal disease, “as reported drug interactions are manageable and venetoclax has a favourable toxicity profile”,  the authors noted.

Similarly, experts backed its use in AML patients treated with midostaurin who have a high risk of fungal infection, but preferably with posaconazole, and conditionally for those with low risk, depending on individual patient factors (neutropenia, history, etc), as well as for those treated with gilteritinib monotherapy.

Antifungal prophylaxis was conditionally recommended in patients receiving ivosidenib as monotherapy, and strongly backed when the drug is administered as part of combination therapy.

The authors also recommended lowering doses of ivosidenib, lestaurtinib, quizartinib and venetoclax while prophylactic triazoles are being administered.

“The risk of developing invasive fungal disease is not excessively high for many novel targeted therapies; however, in combination with intensive chemotherapy or in the relapsed or refractory setting, it can be markedly increased,” the authors said.

“Antifungal prophylaxis with a triazole is crucial in managing patients with acute myeloid leukaemia and is generally recommended during induction treatment, with posaconazole being the drug of choice”, they added.

Looking forward, the authors said individual patient factors prompting initiation of antifungal prophylaxis in the real-world setting need to be established, as well as the role of dosage adjustment of novel antileukaemic drugs when they are administered alongside CYP3A4-inhibiting antifungals, with regard to adverse events and remission.

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