Prophylaxis of Invasive Fungal Infections 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, provides insight on the prevention and treatment of invasive fungal infections in patients with acute myeloid leukemia (AML).

The National Comprehensive Cancer Network (NCCN) Guidelines for prophylaxis currently emphasize the use of azole drugs for the prevention of fungal infections. Previously, fluconazole was the primary recommendation, according to Kieren A. Marr, MD. However, recent data from a randomized trial showed that posaconazole offers a survival advantage over fluconazole. Thus, NCCN gave posaconazole the highest recommendation.

Prophylaxis is crucial for getting ahead of infections, Marr says, and guidelines have evolved over the past few decades. Acyclovir is a nontoxic, but effective drug that prevents herpes reactivation. Other anti-bacterial drugs have been shown in randomized trials to be safe and effective in preventing bacteria-based invasive infections that escape the gut integrity.

Posaconazole is often used prophylactically, according to Marr. Compared with other options, the formulations are better-absorbed and easier to administer. In the allogeneic stem cell transplant population, there are different risk periods (early vs. late). Late infections can occur in the lungs in individuals with graft-versus-host disease. In that setting, physicians can start with a mold-active drug upfront, such as posaconazole or voriconazole, or they can use fluconazole early, and then transition to a mold-active drug.

A number of randomized trials have evaluated azoles for prophylaxis. Itraconazole is associated with toxicities that may outweigh the benefits, especially with regards to gastrointestinal side effects, Marr notes. Voriconazole was not found to be better than fluconazole at preventing or improving fungal-free survival. Posaconazole was evaluated for prophylaxis in two studies and both of them showed some benefits of posaconazole versus fluconazole.