A real-world prospective observational study on the efficacy and safety of liposomal amphotericin B in 426 patients with persistent neutropenia and fever

Abstract

IntroductionInvasive fungal diseases are crucial causes of morbidity and mortality among patients with febrile neutropenia (FN). Though liposomal amphotericin B (L-AMB) is one of the agents recommended for first-line empirical antifungal therapy in patients with FN, large-scale clinical studies have not been performed in Japan. MethodsAn open-label prospective multi-center study was carried out to evaluate the safety and efficacy of L-AMB in Japanese patients with FN suspected of having fungal infection. ResultsOf the 426 patients registered, safety and efficacy evaluations were conducted for 424 and 399, respectively. By clinical response criteria using 5 composite endpoints, the response rate was 46.6% (186/399). The response rate by age were 54.5% (child: 30/55), 47.5% (adult: 97/204), 42.1% (elderly: 59/140) respectively. Regarding the composite endpoints, resolution of fever was observed in 61.2% (244/399), no breakthrough fungal infection in 99.0% (395/399), survival for 7 days or longer after the completion of treatment in 83.7% (334/399), no discontinuation of treatment due to toxicity or lack of efficacy in 60.9% (243/399), and successful treatment of any baseline fungal infection in 10/18. Adverse drug reactions (ADRs) developed in 61.1% (259/424), and frequent ADRs were hypokalemia, kidney dysfunction, and liver dysfunction, as previously reported. ConclusionsThe safety and efficacy profile of L-AMB in Japanese patients with FN suspected of having fungal infection were elucidated for the first time, through the analysis of a large number of cases including pediatric patients under real-world clinical settings collected in this nationwide study.