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Antifungal Prophylaxis for Hematologic Malignancies: Which Agent Is Best?

Invasive fungal infection.

In a meta-analysis evaluating the efficacy of prophylactic agents against invasive fungal infections (IFIs) for patients with hematological diseases, investigators found that posaconazole may be the best option for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), although voriconazole may be the best option for patients undergoing hematopoietic stem cell transplantation (HSCT).

"Invasive fungal infections have emerged as important causes of morbidity and mortality in patients receiving myelosuppressive chemotherapy, immunosuppressive therapy, or HSCT. Because of the difficulty in obtaining a timely diagnosis as well as the high morbidity and mortality associated with IFIs, antifungal prophylaxis remains a high priority," write the investigators in their publication in JAMA Network Open, led by first author Jing Wang, MD, PhD, of the Department of Pathology at Nanjing University Medical School in Nanjing, China. "Over the past decade, clinical benefits from antifungal prophylaxis have been demonstrated. However, there is no clear consensus on antifungal prophylaxis treatment between different centers and groups, particularly in the choice of antifungal prophylaxis agents."

In their network meta-analysis, Dr. Wang and colleagues evaluated the efficacy and safety of antifungal prophylactic agents among patients with hematological disease and in those undergoing HSCT. A total of 14,789 patients who were enrolled in 69 randomized clinical trials were included. All patients received either placebo or one of 11 antifungal prophylactic agents: polyene, conventional amphotericin B, liposomal amphotericin B, miconazole, ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, or micafungin. The primary end points were IFI incidence and mortality, with secondary end points of fungal infections, proven IFIs, invasive candidiasis, invasive aspergillosis, fungi-related death, and withdrawal due to drug-related adverse events.

Compared with placebo, treatment with posaconazole was associated with a significant decrease in the incidence of IFIs (relative risk of 0.57) and invasive aspergillosis infection (relative risk of 0.36). Posaconazole was associated with the greatest probability of success against the development of IFIs (surface under the cumulative ranking curve, 86.7%), followed by caspofungin (84.2%) and micafungin (76.4%). Micafungin was associated with the lowest mortality (surface under the cumulative ranking curve, 90.0%), followed by voriconazole (73.8%) and posaconazole (68.5%). Posaconazole caused the highest incidence of drug withdrawal due to adverse events (surface under the cumulative ranking curve, 17.5%), with voriconazole resulting in the lowest incidence of withdrawal (78.1%). Treatment with voriconazole significantly reduced the incidence of invasive candidiasis compared with placebo, with a relative risk of 0.15. Subgroup analyses ranked voriconazole as the preferred option for patients undergoing HSCT and posaconazole as the preferred option for patients with AML or MDS.

"Our analysis may provide some important information for clinical decision making for antifungal prophylaxis in these patients," conclude Dr. Wang and colleagues. "Our findings suggest that in terms of the prevention of IFIs and tolerance, voriconazole may be the best prophylactic option for patients undergoing HSCT, and posaconazole may be the best prophylactic option for patients with AML or MDS."

For More Information

Wang J, Zhou M, Xu JY, et al (2020). Comparison of antifungal prophylaxis drugs in patients with hematological disease or undergoing hematopoietic stem cell transplantation. JAMA Netw Open, 3(10):e2017652. DOI:10.1001/jamanetworkopen.2020.17652

Image credit: US Centers for Disease Control


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