D-Index–Guided Therapy Reduces Use of Antifungals Without Increasing Infection, Mortality in Febrile Neutropenia

A study has demonstrated that D-index—guided early antifungal therapy (DET), a novel approach to treating persistent or recurrent febrile neutropenia, is feasible in high-risk patients with neutropenia. The study findings, presented as an abstract at the 60th American Society of Hematology Annual Meeting & Exposition, found that DET successfully reduced the use of antifungal agents without increasing invasive fungal infection or mortality compared with empiric antifungal therapy (EAT).

EAT has traditionally been recommended for the treatment of persistent or recurrent febrile neutropenia. However, the treatment has been associated with overtreatment in the majority of these patients. Meanwhile, preemptive treatment as a result of positive blood results for fungal antigens and/or imaging study findings has shown to heighten the incidence of invasive fungal infection, underscoring the importance of a risk-based approach.

“The D-index, which is defined as the area over the neutrophil curve during neutropenia and hence reflects both the duration and depth of neutropenia, enables real-time monitoring of the risk of invasive fungal infection,” explained the researchers.

Previous research has suggested that in high-risk patients with neutropenia, the cumulative D-index produces high negative predictive values for invasive mold infection or pulmonary infection with cutoff values of 5800 or 5500.

Comparing the impact of DET with EAT, the researchers randomized a total of 413 patients who underwent chemotherapy or hematopoietic stem cell transplantation for hematological malignancies and were predicted to have neutropenia lasting more than 7 days. All patients received micafungin 150 mg per day, with patients in the DET group being with preemptive antifungal therapy until the cumulative D-index reached 5500 and antifungal agent being initiated once the cumulative D-index exceeded 5500.

Twelve (6%) patients receiving EAT and 5 (2.4%) patients receiving DET developed invasive fungal infections during the study period. The EAT group experienced 1 case of candidemia and 4 cases of invasive pulmonary aspergillosis, whereas the DET group experienced 1 case of fusariosis.

They researchers noted that the frequency of micafungin use was significantly lower in the DET group compared with the EAT group (32.5% vs 60.2%).

Survival rates were similar between the 2 groups, with a survival rate of 98% in the EAT group and 98.6% in the DET group at day 42. At day 84, the survival rate was 96.4% in the EAT group and 96.2% in the DET group.

According to the researchers, 31 patients died during the safety period from disease progression, infection, or other causes.

Reference

Kimura S, Kanda Y, Lino M, et al. Classical empiric antifungal therapy vs. D-index guided early therapy using micafungin for persistent febrile neutropenia (CEMDIC trial): a randomized controlled trial from Japan FN group study. Presented at 60th American Society of Hematology Annual Meeting & Exposition; December 1, 2018; San Diego, CA. Abstract 816.