Treatment of Invasive Fungal Infection in AML

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In this segment, Kieren A. Marr, MD, professor of medicine in the Johns Hopkins School of Medicine, professor of oncology in the Sidney Kimmel Comprehensive Cancer Center, and medical director of the Transplant and Oncology Infectious Diseases program at Hopkins, highlights the different treatment options for invasive fungal infection in acute myeloid leukemia (AML).

The Infectious Diseases Society of America (IDSA) recently published new guidelines for the treatment of candidiasis which emphasize the use of echinocandins as the primary therapy, according to Kieren A. Marr, MD. Although not yet published, changes to the IDSA aspergillosis recommendations are underway, based on recent clinical trials. The updates will impact primary therapy, salvage therapy, and the role of combining drugs. Currently, monotherapy with voriconazole is the primary treatment for aspergillosis.

In a randomized trial using the combination of voriconazole and anidulafungin, there was close to a 35% improvement in overall survival in the total population, specifically within the AML population. However, the improvement was not statistically significant. Marr notes that, despite this, using two drugs up front in combination is her preferred approach. The trend for improved survival may have been associated with the issues in dosing voriconazole, adds Marr. Many individuals do not achieve the targeted drug levels when using voriconazole as primary therapy. Thus, in this setting, using combination therapy may provide added efficacy.

Isavuconazole is a new azole that has been approved for the treatment of aspergillosis and mucormycosis. For aspergillosis, approval was based on a 600-person randomized noninferiority trial of isavuconazole versus voriconazole in an intent-to-treat analysis, according to Marr. The data showed fewer toxicities, particularly hepatotoxicities, with isavuconazole compared with voriconazole. The approval for treatment of mucormycosis was based on nonrandomized data. The use of isavuconazole varies depending on the facility, whether it is used therapeutically or as a primary or secondary drug. Isavuconazole could be useful in the prophylactic setting, Marr says, adding that she will wait for the safety data prior to using the drug prophylactically.

The challenges for treatment of AML have changed compared with 10 years ago, says Marr. There are multiple drugs in the azole class, as well as new echinocandins, polyenes, and other drugs being developed. More studies need to be done to optimize the use of these drugs for people at risk. It is also important to improve diagnostics, specifically combining tools like the galactomannan assay and the beta-D-glucan assay for more detailed analyses. Improvements are also needed for predicting which azole drug best fits a specific fungal infection in the preventive and treatment realms, especially with fungal infection deaths being in the 20%-to-30% range.