Feasibility and effectiveness of posaconazole prophylaxis in combination with micafungin bridging for patients undergoing allogeneic stem cell transplantation: a 6-yr analysis from the cologne cohort for neutropenic patients

Abstract

Introduction: Invasive fungal diseases (IFDs) are an important cause of morbidity and mortality in patients undergoing allogeneic stem cell transplantation (SCT).

Methods: To compare the effectiveness of two prophylactic antifungal regimens used as standard of care (SOC) in the setting of SCT during the periods of May 2006 - September 2009 (oral posaconazole, POS) and October 2009 - July 2011 (oral posaconazole with intravenous micafungin bridging, POS-MIC), data from the Cologne Cohort of Neutropenic Patients (CoCoNut) study were analyzed after nearest-neighbor matching. Endpoints were occurrence of breakthrough probable/proven IFD under prophylaxis, incidence and duration of persistent febrile neutropenia, incidence of unspecific pneumonic infiltrates, possible IFD, positive galactomannan tests, as well as fungal-free and overall survival.

Results: Of 291 patients with 307 SCTs observed during the study period, 212 fulfilled the inclusion criteria and were included into the analysis. Patients receiving POS-MIC were less likely to develop a pneumonic infiltrate (RR 0.71, 95% CI 0.51-1.00) or possible IFD (RR 0.36, 95% 0.15-0.87). They also demonstrated improved fungal-free survival at day 100 (P = 0.009). No significant differences were observed for the incidence of probable or proven IFD, positive galactomannan tests, persistent febrile neutropenia, duration of hospitalization and overall mortality. There was no grade III or IV CTCAE (Common Terminology Criteria for Adverse Events) toxicity related to antifungal prophylaxis.

Conclusion: Our results suggest that both prophylactic regimens, POS and POS-MIC are feasible, safe and effective. Our data suggest that bridging with intravenous micafungin could indeed improve exposure to antifungal prophylaxis, which may explain the reduced incidence of pneumonia and IFD in the bridging group.

Trial registration: ClinicalTrials.gov NCT01821456.

Keywords: Antifungals; allogeneic stem cell transplantation; aspergillosis; echinocandins; neutropenia; triazoles.