O1-7-1 [Encore]D-index-guided early antifungal therapy for persistent FN in patients with hematological malignancies (CEDMIC trial)

Abstract Introduction Empiric antifungal therapy (EAT) is recommended for persistent febrile neutropenia (FN) based on some large-scale randomized studies. However, EAT sometimes results in overtreatment and unnecessary expense. On the other hand, preemptive therapy triggered by positive fungal tests or radiological findings can increase the incidence of invasive fungal infection (IFI), so an adequate risk-based approach is essential. D-index, recently developed as a parameter reflects both the duration and depth of neutropenia, enables real-time monitoring. We prospectively investigated this novel D-index-guided early antifungal therapy (DET). Methods 423 patients underwent chemotherapy or hematopoietic stem cell transplantation for hematological malignancies were randomized into EAT or DET group, and 413 were eligible for ITT analyses (EAT: 201, DET: 212). The primary endpoint was the incidence of proven/probable IFI. Micafungin at 150 mg/day was administered for FN patients as EAT or DET. Results IFI (proven/probable/possible) was observed in 12 (6.0%) in EAT and 5 (2.4%) in DET, respectively. Proven/probable IFI was identified in 5 (2.5%) of EAT and 1 (0.5%) of DET, which fulfilled the predetermined criteria of non-inferiority of DET group. The survival rate of EAT and DET group was 98.0% vs. 98.6% at day 42 and 96.4% vs. 96.2% at day 84, respectively. The rate of micafungin use was significantly lower in DET group than that in EAT group (29.5% vs. 60.6%, P  Conclusions DET was safe and successfully reduced the use of antifungal agents and total cost. DET is a reasonable alternative strategy for persistent FN.