Voriconazole and Liposomal Amphotericin B (Ambisome) Effectively Prevent Mold Infections in Patients (pts) with Acute Myelogenous Leukemia (AML) Following Remission Induction Chemotherapy (RIC).

Abstract

Invasive fungal infections (IFI) are a frequent cause of morbidity and death in pts with AML and high-risk myelodysplastic syndrome (HR-MDS). Because early diagnosis of IFI is difficult, antifungal prophylaxis (AFP) including mold-active agents has become an important strategy to reduce morbidity and mortality in this patient population and is routinely used at MDACC for AML and HR-MDS pts undergoing RIC. We retrospectively compared the efficacy and safety of 6 AFP regimens (Sept 97- July 04) among 659 evaluable pts with newly diagnosed AML and HR-MDS who received RIC and had been enrolled in our prospective AFP trials. See regimens listed in Table below. There were no significant differences among the 6 regimens with regard to key baseline characteristics (age, gender, diagnosis, cytogenetics, type of RIC, Zubrod PS, WBC count, non-fungal infection and protected environment) and median days of AFP. 37 pts (5.6%) developed IFI (yeast 3 %; mold 2.6%). No mold infections were observed among pts randomized to AMBI or VORI. With the exception of VORI, which was significantly more effective than IV ITRA (p =0.03), all comparisons of efficacy among the AFP regimens were not significant. Drug discontinuation was the highest with IV VORI (21%) and ABLC (18%). VORI was more toxic than IV ITRA, Caspo, and F+I (p=0.023, 0.001 and 0.031 respectively). VORI toxicity was reversible and consisted of visual and/or auditory hallucinations and elevation in serum bilirubin. There was a trend toward developing VORI toxicity if baseline bilirubin levels were elevated (OR=4.9; p=0.10).We conclude that the rate of IFI in AML and HR-MDS pts undergoing RIC given mold-active AFP is 5.6 %. VORI and AMBI effectively prevented mold infections. VORI was more effective that IV ITRA but was associated with a high rate of reversible drug-related adverse events.ABLC (n=131)AMBI (n=69)F+I (n=67)IV ITRA (n=225)CASPO (n=106)VORI (n=61)Median age, years (range)65(21–87)63(36–83)57(19–84)62(17–89)65(22–82)59(23–79)Zubrod ≤ 2 (%)127(97)69(100)65(97)214(95)101(95)61(100)Median days AFP (range)17(3–32)14(3–28)16(3–44)20(3–41)21(3–38)21(3–34)Breakthrough IFI (%)7(5)3(4)3(5)17(8)7(7)0 Yeast (%)2(2)3(4)1(1)11(5)3(3)0 Mold (%)5(4)02(3)6(3)4(4)0Drug-related AFP DC (%)24(18)10(14)5(7)23(10)4(4)13(21)ABLC: Amphotericin B Lipid Complex: 2.5 mg/kg IV three times/week;AMBI: Liposomal Amphotericin B: 3 mg/kg IV three times/week;F+I: Fluconazole: 400 mg (tab)/d + Itraconazole: 200 mg (caps)/d;IV ITRA: IV itraconazole: 200 mg BID X 2 d, then 200 mg IV/d;CASPO: Caspofungin: 50 mg IV/d;VORI: Voriconazole: 400 mg IV BID x 2 d, then 300 mg IV BID.