Comparison of Micafungin and Liposomal Amphotericin B for Empirical Antifungal Therapy in Febrile Neutropenic Patients with Acute Myeloid Leukemia: A Randomized Controlled Trial

Tatsuo Oyake 1, Yuka Fujisawa 1,2, Norifumi Sugawara 1,3, Ryousei Sasaki 1,3, Wataru Izumita 4, Takahiro Mine 5, Maki Asahi 1, Yuzo Suzuki 1, Yoshiaki Okano 1, Yukiteru Fujishima 1, Yasuhiko Tsukushi 2, Yusei Aoki 1, Shugo Kowata 1, Ichiro Hanamura 6, Kazunori Murai 7, Shigeki Ito 8 and Yoji Ishida 1

Author address: 

1Division of Hematology, Department of Internal Medicine, Iwate Medical University School of Medicine, Morioka, Japan 2Division of Hematology, Department of Internal Medicine, Hachinohe Red Cross Hospital, Hachinohe, Japan 3Division of Hematology, Department of Internal Medicine, Iwate Prefectural Chubu Hospital, Kitakami, Japan 4Division of Hematology, Department of Internal Medicine, Iwate Prefectural Ohfunato Hospital, Ohfunato, Japan 5Division of Hematology, Department of Internal Medicine, Morioka Red Cross Hospital, Morioka, Japan 6Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute, Japan 7Division of Hematology, Department of internal Medicine, Iwate Prefectural Central Hospital, Morioka, Japan 8Department of Medical Oncology, Iwate Medical University School of Medicine, Morioka, Japan

Abstract: 

Background: Invasive fungal infections (IFIs) incur significant morbidity and mortality in neutropenic patients with hematological malignancies (HEM) after chemotherapy. The risk for these infections is related to the intensity and duration of neutropenia, and varies from 2% to 40%. Mortality rates associated with documented IFIs are considerable, reportedly ranging from 30% to 60%. Empirical antifungal therapy is the standard care for neutropenic patients with HEM, who remain febrile despite broad-spectrum antibacterial treatment. Several antifungal agents including voriconazole (VRCZ) or liposomal amphotericin B (L-AMB) have been studied as empirical therapy for febrile neutropenia (FN). However, limited data are available concerning the efficacy of micafungin (MCFG) in FN patients with acute myeloid leukemia (AML). Methods: We conducted a randomized, cooperative group, open-label trial comparing MCFG (150 mg once daily) with L-AMB (2.5 mg/kg once daily) as a first-line empirical antifungal treatment for 102 hospitalized FN patients with AML (MCFG, 53; L-AMB, 49). The efficacy end point was a favorable overall response, as determined by a five-component end point according to the criteria of Walsh et al (N Engl J Med 2004; 351: 1391). Results: At the time of enrolment, there were no significant differences in the demographics or baseline characteristics between the two groups. The mean treatment duration for MCFG and L-AMB was 14.8 and 17.1 days, respectively. The efficacy rates of MCFG and L-AMB were not significantly different (58.5% vs. 44.9%, p = 0.1698*), evaluated based on: (1) successful treatment of baseline fungal infection (3/5cases (5.7%) vs. 0/1case (0%), p = 0.170*), (2) absence of breakthrough fungal infection (90.6% vs. 98.0%, p = 0.112*), (3) survival for ≥7 days after study completion (88.7% vs. 89.8%, p = 0.855*), (4) absence of premature study drug discontinuation due to poor efficacy or drug-related adverse events (67.9% vs. 75.5%, p = 0.396*), and (5) resolution of fever during neutropenia (66.0% vs. 55.1%, p = 0.258*). However, discontinuation due to drug-related adverse events occurred less frequently in the MCFG group (1.9% vs. 12.2%, p = 0.038*). In safety evaluation, adverse events of creatinine increase and hypokalemia were less often in the MCFG group than in the L-AMB group (9.4% vs. 26.5%, P=0.023*, 22.6% vs. 57.1%, P=0.0004*). *: Chi square test. Conclusions: MCFG was as effective as L-AMB, and better tolerated than L-AMB as an empirical antifungal therapy in FN patients with AML.

2016

abstract No: 

1607

Full conference title: 

58th American Society of Hematology Annual Meeting 2016
    • ASH 58th (2016)