Combination therapy with efungumab for the treatment of invasive Candida infections: several illustrative case reports

Introduction

Efungumab (Mycograb^®) is a human recombinant antibody against fungal Hsp90 that, in combination with lipid-associated amphotericin B, has shown efficacy in patients with invasive candidiasis (phase 3 data). Eight compassionate-use case studies of efungumab in combination with antifungal agents in the treatment of invasive Candida infections are presented.

Methods

Efungumab was given to eight patients at 1 mg/kg twice daily, typically for 5 days combined with standard doses of amphotericin B, caspofungin, flucytosine or fluconazole. Patients were 7–69 years old with culture-confirmed invasive fungal infections, from which Candida spp. (Candida albicans, Candida krusei, Candida glabrata) were isolated; five patients had candidal peritonitis, one candidaemia, one a subphrenic abscess and candidaemia, and one mediastinal, pleural and pulmonary candidiasis; one patient had neutropenia.

Results

Seven out of eight patients responded to 10 doses of efungumab; one patient (a child with candida peritonitis and abdominal abscesses associated with a non-Hodgkin's abdominal lymphoma) responded but relapsed and required a second course of treatment, to which he responded. One patient, with mediastinal, pulmonary and pleural candidiasis associated with ARDS, was withdrawn after two doses of efungumab, due to blood pressure fluctuations, impaired gas exchange, increased cardiac output and fever; in this patient the efungumab was not prefiltered. Three further patients experienced transient hypotensive or hypertensive episodes after the first dose, which did not recur with subsequent doses. One patient experienced nausea and vomiting after the second dose.

Conclusion

This experience with efungumab extends the clinical trial database. It shows efficacy in poor-prognosis patients who failed to respond to conventional monotherapy (6–20 days), in patients with multiple species of Candida, and in candidaemia in a neutropenic patient. All but one patient tolerated efungumab and seven patients completed the course without major side effects.