Micafungin Versus Fluconazole Or Itraconazole For Prophylaxis Against Invasive Fungal Infections During Neutropenia In Patients Undergoing Haplo-Identical Hematopoietic Stem Cell Transplantation

el-Cheikh Jean, Crocchiolo Roberto, Fürst Sabine, Bramanti Stefania, Sarina Barbara, Granata Angela, Faucher Catherine, Mohty Bilal, Bouabdallah Reda, Norbert Vey, MD, Christian Chabannon, MD, PhD, Santoro Armando, Blaise Didier, Castagna Luca, Harbi Samia, and Didier Blaise, MD.

Abstract: 

Objectives Over the past decade, invasive fungal infections (IFI) have remained an important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined.

Patients and Methods we conducted a retrospective, bi-institutional comparative clinical study, (Institut Paoli-Calmettes at Marseille France and Humanitas cancer center at Rozzano, Italy), and we compared the efficacy and safety of Micafungin 50mg/day (iv) with those of fluconazole (400mg/day) or itraconazole 200mg/day (iv) as prophylaxis for adult patients with various haematological diseases receiving haplo-identical allogeneic stem cell transplantation (haplo-SCT). Patients received prophylaxis with the beginning of the transplant conditioning regimen until the hospital discharge, or until occurrence of an IFI. We compared the incidence of proven or probable IFI (the primary end point) between the micafungin and fluconazole or itraconazole groups; death from any cause and time to death was secondary end points. Patients were followed for 100 days after haplo-SCT and for 30 days after the last dose of the prophylaxis drug administrated.

Results From January 2009 to May 2013, a total of 99 patients were identified; 30 patients received micafungin, and 69 patients received fluconazole or itraconazole. 81 patients (82%) received a non myeloabaltive conditioning regimen (NMA), with Fludarabine, Cyclophosphamide and Total body irradiation (TBI) 2 Gy based , or Fludarabine, Busulfan, and Cyclophosphamide based (3%) or other (9%), while five patients (5%) received a thiotepa-based conditioning regimen. The patients and transplant details are shown in the table 1. Proven or probable invasive fungal infections were reported in 2 patients (7%) in the micafungin group and 8 patients (12%) in the fluconazole or itraconazole group (absolute reduction in the micafungin group, −5%; 95% confidence interval, 0.0565-3.1395, P=0.72). Fewer patients in the micafungin group had invasive aspergillosis (1 [3%] vs. 5 [7%], P=0.6). A total of 4 (13%) patients in the micafungin group and 23 (33%) patients in the fluconazole or itraconazole group received empirical antifungal therapy (P = 0.14).

Table 1

Patient and transplantation characteristics:

                                                                                                                        

No serious adverse events related to treatment were reported by patients and there was no treatment discontinuation because of drug related adverse event in both groups.

Overall Survival and disease free survival were similar among the two groups (P = 0.97). 6 patients (20%) in the micafungin group died within 100 days, as did 10 patients (14%) in the fluconazole or itraconazole group (P = 0.57). Interestingly the transplant related mortality (TRM) at 100 days was 0% in the micafungin group vs 13% in the second group [CI 95% (0-22)] (p=0,06), whereas the relapse or progression rate at 100 days was 27% vs. 8% respectively [CI 95% (14-44)] (p=0,14).

Conclusions In patients undergoing to haplo-SCT, antifungal prophylaxis with micafungin is well tolerated and effective to prevent IFI. Furthermore, the incidence of IFI and invasive aspergillosis seems lower even if this did not attend statistical power, probably due to low number of patients.

    • ASH 55th (2013)