Efficacy and Safety of Micafungin for Prophylaxis of Invasive Fungal Infections in Patients Undergoing Haplo-Identical Hematopoietic Stem Cell Transplant

Abstract 4505

Invasive fungal infections (IFI) such as candidiasis and mold infections cause significant morbidity and mortality among immunocompromised patients in recent years. Micafungin, a new echinocandin, inhibits fungal cell wall beta-glucan synthesis, with potent activity against most species of Candida and Aspergillus.

The aim of this observational study was to investigate the efficacy and safety of Micafungin in prophylaxis of invasive fungal infections (IFI) in 20 high risk adult patients with various haematological diseases receiving haplo-identical allogeneic stem cell transplantation (Allo-SCT). Treatment success was defined as no proven, probable, or suspected IFI through therapy and the absence of proven or probable IFI through the end of 12 weeks after therapy. (EORTC criteria).

These patients were monitored after Allo-SCT for galactomannan antigenemia at least once per week, and a computed tomography (CT) scan was performed in the case of persistent fever for at least 5 days after broad-spectrum empirical antibacterial therapy. Routine controls (e.g. detection of galactomannan antigenemia and CT scan) were performed systematically after 1 and 2 months and on day 100 after Allo-SCT.

Only 2 patients had a history of possible aspergillosis before transplant treated by voriconazole. The patients received a median of 4 lines (2–7) of treatments before Allo-SCT. Ten patients (50%) received at least one auto-SCT; and 5 patients (25%) received a previous Allo-SCT. 18 patients (90%) received a reduced intensity conditioning regimen (RIC), with Fludarabine, Cyclophosphamide and Total body irradiation (TBI) 2 Gy based (75%), or Fludarabine, Busulfan, and Cyclophosphamide based (10%) or other (5%). while two patients (10%) received a myeloablative conditioning regimen with thiotepa. The patients and transplant details are shown in the table 1.

Patients received a median of 26 infusions (range, 1–8) of Micafungin (50 mg/day i.v. as a 1h infusion). The treatment was initiated at the beginning of the transplant conditioning regimen until the hospital discharge. None of our patients discontinued the treatment for drug-related adverse events. Micafungin was not associated with any hepatotoxicity. Only one patient (5%) discontinued the treatment because an early disease progression.

At last follow-up, there are 17 patients (85%) who are alive, with a median follow-up of 6 months (3–17). Three patients (15%) dead because disease progression.

In all patients no candidas and/or Aspergillus species was documented after 3 and 6 months from transplant. None of our patients presented a positive galactomannan antigenemia >0.5. Seven patients (35%) presented a CMV reactivation. Only one patient presented an acute GvHD grade II.

Micafungin has a good safety and tolerability profile, with an efficacy in preventing IFI in this high risk population. Our data provide support for an efficacy study in a prophylaxis setting, but prospective and comparative clinical trials using Micafungin are urgently needed to define the role of this drug in prophylaxis after haplo-identical Allo-SCT.