The effectiveness of liposomal amphotericin in the treatment of invasive fungal infections is not affected by prior azole administration: the Ambi-Prof study

J. de la Serna, I. Jarque, J. López, R. Mar, V. Gómez-Garcí­a, J. Serrano, A. Báez, A. Sampol, P. Amat, C. Barrenetxea, R. del Campo, J. Garcí­a, M. Jurado on behalf of the Study Group of Liposomal Amphotericin B

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It is a matter of debate whether mold-active azole prophylaxis may reduce the effectiveness of Liposomal Amphotericin (L-AmB). Objectives: This retrospective study was aimed to determine the non-inferiority of prior azole administration in the treatment of Invasive Fungal Infections (IFI) with L-AmB in hematologic and allogeneic HSCT patients. Methods: Patients who met the EORTC/MSG criteria for IFI and received treatment with L-AmB were eligible and distributed in two arms according to: (A) mold-active azole exposure prior to L-AmB, and (B) fl uconazole or no prior azole. Patients were stratifi ed according to the type of IFI and evaluated for disease related risk factors and comorbidities. The primary endpoints were favorable response and survival at the end of antifungal therapy, at 4 and 12 weeks. Results: From Feb/2008 to Sep/2009, 182 consecutive patients were recruited from 26 institutions. The median age was 45 years (range 1-78). Most had acute leukemia (AL) or myelodysplasia (MDS) (129; 70.0%). Baseline disease was treated for induction, in remission, or refractory/relapse status in 23.6%, 45.0% and 31.4%, respectively. A 40.1% of patients had allogeneic HSCT. Severe comorbidity and prior IFI were present in 20.3% and 14.8%, respectively. Arm A included 100 patients with prior itraconazole 39%, voriconazole 35% and posaconazole 26%. Arm B included 82 patients with fl uconazole 49% or no azole 51%. Patients characteristics were not different in both arms, except for more AL or MDS (P = 0.002) and prolonged neutropenia in arm A (P = 0.021), and more use of high dose steroids in arm B (P = 0.01). The rates of possible, probable and proven IFI were 52.7%, 28.6% and 18.7%, respectively (Table 1). Aspergillosis was the proven IFI in 28 of 35 cases. L-AmB was given 3 mg/kg/d for a median of 18 ± 17 days in A and 15 ± 13 in B. The favorable response rate to LAmB was 75% and 74.4% in both groups, with no differences in the responses at the end of treatment, at 4 weeks or at 12 weeks. The response rates for possible and probable/proven IFI were similar in both groups (Table 2). Conclusions: Prior exposure to mold-active azoles does not affect the effectiveness of L-AmB for the treatment of IFI in this high risk patient population, indicating that concerns for sequential administration are no longer justifi ed.

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Annual Meeting of the EBMT, 36th
    • EBMT 36th (2010)