NYMC Faculty Publications

Title

Dinutuximab in the Treatment of Neuroblastoma

Document Type

Article

Publication Date

2-15-2017

Department

Pediatrics

Abstract

Introduction: Neuroblastoma is the cancer of the sympathetic nervous system. Nearly half of the patients with neuroblastoma present with high-risk features and have poor outcome despite aggressive therapy. The high expression of GD2 - a cell surface disialoganglioside - in neuroblastoma and its restricted distribution in normal tissues make anti-GD2 monoclonal antibodies suitable for immunotherapy. Areas covered: Dinutuximab is an anti-GD2 monoclonal antibody which is a chimeric construct composed of the variable region heavy and light chain genes of the murine mAb14.G2a and the human constant region genes for heavy chain IgG1 and light chain kappa. Dinutuximab is a unique orphan drug, that was approved by the FDA on 3/10/2015 for use in high-risk neuroblastoma patients who achieve at least a partial response to prior first-line multiagent, multimodality therapy in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), aldesleukin (interleukin-2 [IL-2]), and isotretinoin. The author examines the published pharmacokinetic, safety and efficacy data from the Phase I/II/III studies. Expert opinion: Although dinutuximab has significant side-effects such as neuropathic pain, hypersensitivity reactions, fever, hypotension and capillary leak, its use when combined with GM-CSF, IL-2 and isotretinoin has led to improvements in event-free survival (EFS) and overall survival (OS) in high-risk neuroblastoma patients who have responded to the standard front-line multiagent, multimodality treatment.

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