Study Identifies Best Prophylaxis Option for Patients Undergoing HSCT and with AML or MDS

Findings published in JAMA Network Open suggested that voriconazole (Vfend) may be the best prophylaxis option for patients undergoing hematopoietic stem cell transplantation (HSCT), and posaconazole (Noxafil) may be the best prophylaxis option for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

“Because of the difficulty in obtaining a timely diagnosis as well as the high morbidity and mortality associated with [invasive fungal infections; IFIs], antifungal prophylaxis remains a high priority in these populations at high risk of IFIs. However, there is no clear consensus on antifungal prophylaxis treatment between different centers and groups, particularly in the choice of the antifungal prophylaxis agents,” the authors wrote.

“We performed a systematic review and network meta-analysis to gain a better understanding of the outcomes associated with and tolerance to current antifungal agents,” they added.

Researchers searched Medline, EMBASE, and the Cochrane Central Register of Controlled Clinical Trials to collect all relevant data from randomized clinical trials that assessed antifungal prophylaxis in patients with hematological disease. Specifically, 69 studies that compared any antifungal agent with a placebo, no antifungal agent, or another antifungal agent among patients with hematological disease or patients who were undergoing HSCT were included. Overall, 14,789 patients were among the trials included and 12 treatments were compared.

The co-primary end points for the study were IFIs and mortality. Key secondary end points included fungal infections, proven IFIs, invasive candidiasis, invasive aspergillosis, fungi-related death, and withdrawal owing to adverse effects of the drug.

Ultimately, posaconazole was the treatment found to be correlated with the best probability of success against IFIs (surface under the cumulative ranking curve, 86.7%; mean rank, 2.5).

Compared with placebo, posaconazole treatment was associated with a significant reduction in IFIs (RR, 0.57; 95% CI, 0.42-0.79) and invasive aspergillosis (RR, 0.36; 95% CI, 0.15-0.85). Moreover, voriconazole was associated with a significant reduction in invasive candidiasis (RR, 0.15; 95% CI, 0.09-0.26) compared with placebo. However, treatment with posaconazole was correlated with a higher incidence of withdrawal due to the adverse effects of the agent (surface under the cumulative ranking curve, 17.5%; mean rank, 9.2).

“Overall, posaconazole and voriconazole are recommended as the most reasonable options for the prevention of IFIs,” the authors noted. “The difference between agents may be meaningful and is not available from single trials, to our knowledge. For instance, voriconazole has not been directly compared with other drugs except for placebo, fluconazole, and itraconazole; however, this network meta-analysis compared voriconazole, as well as posaconazole, with other drugs indirectly.”

In subgroup analyses which considered efficacy and tolerance, voriconazole was suggested to be the best choice for patients undergoing HSCT, especially those undergoing allogenic HSCT. However, posaconazole was ranked as the best option for patients with AML or MDS.

Importantly, though this subgroup analyses found different results among different patient populations, the data did not allow investigators to perform more detailed analyses, such as those for different ages and races/ethnicities. In addition, researchers could not perform a more stratified analysis taking into consideration the dosage form and dose of agents. Thus, the results from this meta-analysis should be taken with caution for shared decision-making.

Moving forward, the investigators indicated these study findings should aid in the design of future practice-changing prospective trials.

Reference:

Wang J, Zhou M, Xu J, Zhou R, Chen B, Wan Y. Comparison of Antifungal Prophylaxis Drugs in Patients With Hematological Disease or Undergoing Hematopoietic Stem Cell Transplantation. JAMA Network Open. doi: 10.1001/jamanetworkopen.2020.17652