Information about Dinutuximab
Liver safety of Dinutuximab
Transient asymptomatic elevations in serum aminotransferase levels are common during dinutuximab therapy, but it has not been linked to instances of clinically apparent liver injury.
Mechanism of action of Dinutuximab
Dinutuximab (din" ue tux' i mab) is a mouse-human chimeric monoclonal IgG1 antibody to disialoganglioside (GD2), a cell surface glycolipid that is present in low concentrations on skin, neural or peripheral nerve cells and is overexpressed on neuroblastoma cells. Engagement of dinutuximab with GD2 triggers antibody dependent cell cytotoxicity. Cytotoxicity of dinutuximab is increased by coadministration of granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin 2 (IL2) because of their effects on neutrophils, macrophages and immune effector cells, for which reason dinutuximab is usually combined with these cytokines.
FDA approval information for Dinutuximab
Dinutuximab was approved for use in neuroblastoma in the United States in 2015. Current indications are for its administration with IL2 or GM-CSF added to standard isotretinoin therapy of high risk pediatric patients with neuroblastoma.
Dosage and administration for Dinutuximab
Dinutuximab is available in liquid solution in single use vials of 17.5 mg in 5 mL (3.5 mg/mL) under the brand name Unituxin. Dinutuximab is given by slow intravenous infusion (over 10 hours) in a dose of 17.5 mg/m2 daily for 4 consecutive days, repeated in up to 5 cycles. Premedication with hydration, diphenhydramine, acetaminophen and a potent analgesic [such as morphine] is recommended.
Side effects of Dinutuximab
Adverse side effects of the combination immunotherapy are frequent and can be severe. These side effects include infusion reactions, nausea and vomiting, rash, hypotension, capillary leak syndrome, neuropathic pain and peripheral neuropathy. Less common, but potentially severe side effects include severe hypersensitivity reactions, neurologic and ophthalmologic toxicities, transverse myelitis, reversible posterior leukoencephalopathy syndrome, severe infections, bone marrow suppression, electrolyte abnormalities and embryo-fetal toxicity.