ABSTRACT
BACKGROUND: Daratumumab, a first-in-class humanized IgG1κ monoclonal antibody that targets the CD38 epitope, has been approved for treatment of multiple myeloma by FDA. The current study was to evaluate daratumumab-related adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS: Disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were employed to quantify the signals of daratumumab-associated AEs. RESULTS: Out of 10,378,816 reports collected from the FAERS database, 8727 reports of daratumumab-associated AEs were identified. A total of 183 significant disproportionality preferred terms (PTs) were retained. Unexpected significant AEs such as meningitis aseptic, leukoencephalopathy, tumor lysis syndrome, disseminated intravascular coagulation, hyperviscosity syndrome, sudden hearing loss, ileus and diverticular perforation were also detected. The median onset time of daratumumab-related AEs was 11 days (interquartile range [IQR] 0-76 days), and most of the cases occurred within 30 days. CONCLUSION: Our study found potential new and unexpected AEs signals for daratumumab, suggesting prospective clinical studies are needed to confirm these results and illustrate their relationship.
Subject(s)
Adverse Drug Reaction Reporting Systems , Antibodies, Monoclonal , Databases, Factual , Multiple Myeloma , Pharmacovigilance , United States Food and Drug Administration , Humans , Adverse Drug Reaction Reporting Systems/statistics & numerical data , United States , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/administration & dosage , Multiple Myeloma/drug therapy , Male , Female , Middle Aged , Aged , Data Mining , Antineoplastic Agents/adverse effects , Antineoplastic Agents/administration & dosage , Adult , AlgorithmsABSTRACT
Self-assembly of peptides is closely related to many diseases, including Alzheimer's, Parkinson's, and prion diseases. Understanding the basic mechanism of this assembly is essential for designing ultimate cure and preventive measures. Template-assisted self-assembly (TASA) of peptides on inorganic substrates can provide fundamental understanding of substrate-dependent peptides assemble, including the role of hydrophobic interface on the peptide fibrillization. Here, we have studied the self-assembly process of a potential pentapeptide inhibitor on the surface of highly oriented pyrolytic graphite (HOPG) using real time atomic force microscopy (RT-AFM) as well as molecular dynamics (MD) simulation. Experimental and simulation results show nanofilament formation consisting of ß-sheet structures and epitaxial growth on HOPG. Height analysis of the nanofilaments and MD simulation indicate that the peptides adopt a lying down configuration of double-layered antiparallel ß-sheets for its epitaxial growth, and the number of nanofilament layers is concentration-dependent. These findings provide new perspective for the mechanism of peptide-based fibrillization in amyloid diseases as well as for designing well-ordered micrometrical and nanometrical structures.
