Primary Fungal Prophylaxis in Hematological Malignancy: a Network Meta-Analysis of Randomized Controlled Trials

Several new antifungal agents have become available for primary fungal prophylaxis of neutropenia fever in hematological malignancy patients. Our aim was to synthesize all evidence on efficacy and enable an integrated comparison of all current treatments. We performed a systematic literature review to identify all publicly available evidence from randomized controlled trials (RCT). We searched Embase, PubMed, the Cochrane Central Register of Controlled Clinical Trials, and the www.ClinicalTrials.gov website. In total, 54 RCTs were identified, including 13 treatment options. The evidence was synthesized using a network meta-analysis. Relative risk (RR) was adopted. Posaconazole was ranked highest in effectiveness for primary prophylaxis, being the most favorable in terms of (i) the RR for reduction of invasive fungal infection (0.19; 95% confidence interval [CI], 0.11 to 0.36) and (ii) the probability of being the best option (94% of the cumulative ranking). Posaconazole also demonstrated its efficacy in preventing invasive aspergillosis and proven fungal infections, with RR of 0.13 (CI, 0.03 to 0.65) and 0.14 (CI, 0.05 to 0.38), respectively. However, there was no significant difference among all of the antifungal agents in all-cause mortality and overall adverse events. Our network meta-analysis provided an integrated overview of the relative efficacy of all available treatment options for primary fungal prophylaxis for neutropenic fever in hematological malignancy patients under myelosuppressive chemotherapy or hematopoietic cell transplantation. On the basis of this analysis, posaconazole seems to be the most effective prophylaxis option until additional data from head-to-head randomized controlled trials become available.