An overview of EHA guidelines for the use of antifungal prophylactic agents in acute myeloid leukemia

With increasing diversity of advances in the treatment of acute myeloid leukemia (AML), the need for prophylaxis against infection has also evolved. Triazoles currently serve as the cornerstone antifungal agent during remission reduction chemotherapy treatment of AML. However, there is always a possibility of the development of complications due to drug-drug interaction caused by CYP3A4 inhibition.

In 2019, a joint initiative was taken by European Hematology Association (EHA) Scientific Working Group (EHA SWG) Infections, EHA SWG AML, and Cochrane Hematology Group to propose a guideline on antifungal prophylaxis (AFP) for patients with AML treated with novel agents. An updated outline of this guideline was provided by Jannik Stemler in his presentation during the EHA2021 Virtual Congress.¹

Methods adapted for guideline preparation

The following methods were used for the guideline preparation:

• The committee included experts from Europe and Israel.
• In the selection of novel available AFP agents, consideration was given to the available drugs that are licensed or are under clinical trial investigation as monotherapy or combination treatment.
• A systematic review of the literature, followed by evidence and consensus-based recommendations (using the GRADE approach), was used to provide the first guidance on AFP in this setting.
• Strong recommendations were given dependent on the availability of strong clinical data. Where the evidence is limited, weak/conditional recommendations were made.

Recommendations

The use of existing guidelines was recommended when using antifungal prophylactic agents. Where the evidence is limited, consideration should be given to individual patient factors and the clinical setting to decide on the appropriate antifungal agents. The risk of potential toxicity and drug-drug interaction in the specific patient population and whether a strong inhibitor is present should also be considered. A list of selective AFP agents, along with the recommendations by EHA, is given in Table 1.

Table 1. Selective AFP agents and usage recommendations*

Conclusion

EHA guidelines for the use of antifungal prophylactic agents suggest that selection of an agent should be based on finding the right balance between the risk of fungal infection, toxicity, and drug-drug interaction. For many of the antifungal agents listed, the evidence is scarce and only weak recommendations can be made. Nevertheless, this represents the first guidance on AFP management in the context of patients with AML receiving novel agents, which could assist healthcare professionals and oncologists in their treatment decisions.