(284) Retrospective Cross-Sectional Study Assessing Adverse Events And Treatment Failure In Pediatric Hemato-Oncological Patients Receiving Posaconazole (Off-label) Or Liposomal Amphotericin B Prophylaxis

Background: Pharmacological primary prophylaxis plays an essential role in prevention of invasive fungal infections (IFI). Posaconazole is an important prophylactic option in managing IFIs and recently approved in children older than 2 years old.

Objectives: This study aimed at assessing the differences in the risk of experiencing an adverse event or treatment failure between posaconazole and Liposomal amphotericin B (L-amB) in prophylactic regimens.

Methods: This retrospective cross-sectional study spanning from January 2017 to November 2021 was conducted at the Onco-hematological pediatric department in Padua included all patients aged three months to 21 years receiving posaconazole or L-amB 5 mg/kg twice weekly in prophylactic regimens. Children were followed up for 10 or 12 months depending on the primary disease (ALL-acute lymphoblastic leukemia or other malignancies) or the end of the prophylaxis, whichever came first. Primary outcomes included any adverse event and IFI diagnosed after the start of the prophylactic regimens or the achievement of the therapeutic dosage (posaconazole only). We calculated for both ALL and other malignancies groups, the outcomes cumulative incidence of the two prophylactic regimens using the Kaplan-Meier estimator and assessed significant difference using a log-rank test. Hazard Ratios (HR) with 95% confidence intervals were estimated with Cox-regression models.

Results: Overall, 51 and 37 patients received posaconazole and L-amB as prophylaxis, respectively. Both children with ALL and with other malignancies receiving posaconazole, had a lower probability of experiencing an adverse event compared to the Lam-B group (27% vs 74%, log-rank test p< 0.001 and 17% vs 49%, log-rank test p< 0.001) 10 and 12 months after the prophylaxis start, respectively. Overall, children receiving posaconazole prophylaxis had a 93 and 95% lower risk of experiencing an adverse event compared to the Lam-B group in (ALL: HR:0.07[95%CI:0.01-0.43], Cox-model p=0.004; other malignancies HR:0.05[95%CI:0.00-0.53], Cox-model p=0.013). No difference in the probability of experiencing an IFI was noted among the two groups.

Conclusions: Prophylaxis with posaconazole was associated with fewer adverse events in comparison with the Lam-B group. Given the similar risk of prophylaxis failure, posaconazole can be considered a good alternative to the Lam-B prophylaxis.