Abstract
Optimal clinical care and clinical investigation of patients with mucormycosis are limited by absence of controlled trials, and absence of well-defined predictors of mortality or clinical response. The Deferasirox-AmBisome Therapy for mucormycosis (DEFEAT Mucor) study was the first randomized clinical trial conducted on patients with mucormycosis, and demonstrated that adjunctive deferasirox therapy did not improve outcomes of the disease. The current study describes clinical factors from the 20 patients enrolled to identify those associated with 90-day mortality of the 11 (55%) patients who died by day 90. Age, diabetes mellitus, transplant status, or antifungal therapy were not associated with mortality. However, active malignancy or neutropenia at enrollment were associated with increased mortality. Pulmonary infection was linked with lower Kaplan-Meier survival compared to non-pulmonary infection. Higher baseline serum concentrations of iron and ferritin were also associated with mortality. No patient who progressed clinically during the first 14 days of study therapy survived; however, many patients who clinically improved during that time did not survive to 90 days. In contrast, day 30 clinical response was predictive of 90-day survival. These factors may be useful in defining enrollment randomization stratification critieria for future clinical trials, and in supporting clinical care of patients with mucormycosis.
Acknowledgements
This study was funded by investigator-initiated grants from Novartis, Gilead, and Astellas to Brad Spellberg. The study was sponsored by the Los Angeles Biomedical Research Institute, a non-profit 501c research institute. Neither the funding companies nor the Los Angeles Biomedical Research Institute had any input on study design, conduct, or analysis, or the drafting of this manuscript.
Declaration of interest: BS received grant support from Gilead, Novartis, and Astellas to fund the DEFEAT Mucor study. Funding companies played no role in study design, interpretation, or drafting of the manuscript. DPK has received research support and honoraria from Merck, Fujisawa, Enzon, Pfizer, and Schering-Plough. MIM has served on advisory boards for Astellas, Pfizer, and Merck and received research funding from Astellas, Basilea, and Pfizer. She has been a member of the speaker's bureaus of Astellas and Pfizer. JP has had research grants/consulting/honorariums from Merck, Enzon, Astellas, and Pfizer. ASI has received grants from Astellas, Enzon, Merck, Novartis, and Pfizer. EPB was partially compensated from the Gilead, Novartis and Astrellas funds for his time related to the DEFEAT study. In addition, in the past 12 months EPB has served as a consultant to: Sigma Tau Pharmaceuticals, Merck, GlaxoSmithKline, Novartis, Kowa Research Institute, Worldwide Clinical Trials, Novo Nordisk, Catabasis Pharmaceuticals, 3D Communications, Consumer Healthcare Products Association, Allergan, Medtronic, Amgen, PEGUS Research, World Self-Medication Industry, Optimer Pharmaceuticals, Gen-Probe Incorporated, McNeil Pharmaceuticals, Bayer, Endo Pharmaceuticals, Orexigen Therapeutics, Arena Pharmaceuticals, Nektar Therapeutics, AtriCure and Talon Therapeutics. DF and PVC have no disclosures. The authors alone are responsible for the content and the writing of the paper.
This paper was first published online on Early Online on 23 March 2012.