Abstract
Prognosis of metastatic neuroblastoma is very poor. Its treatment includes induction chemotherapy, surgery, high-dose chemotherapy, radiotherapy, and maintenance with retinoic acid, associated with the anti-GD2 monoclonal antibody (ch14.18) dinutuximab. Immunotherapy determined a significant improvement in survival rate and is also utilized in relapsed and resistant neuroblastoma patients. Five courses of dinutuximab 100 mg/m2 are usually administered as a 10-day continuous infusion or over 5 consecutive days every 5 weeks. Dinutuximab targets the disialoganglioside GD2, which is highly expressed on neuroblastoma cells and minimally present on the surface of normal human neurons, peripheral pain fibers, and skin melanocytes. Anti GD2 antibodies bind to surface GD2 and determine the lysis of neuroblastoma cells induced by immune response via the antibody-dependent cellular cytotoxicity and the complement-dependent cytotoxicity. Dinutuximab has significant side effects, including neuropathic pain, peripheral neuropathy, hypersensitivity reactions, capillary leak syndrome, photophobia, and hypotension. The most important side effect is neuropathic pain, which is triggered by the same antibody–antigen immune response, but generates ectopic activity in axons, which results in hyperalgesia and spontaneous pain. Pain can be severe especially in the first courses of dinutuximab infusion, and requires the administration of gabapentin and continuous morphine infusion. This paper will focus on the incidence, mechanisms, characteristics, and treatment of neuropathic pain and peripheral neuropathy due to dinutuximab administration in neuroblastoma patients.
Highlights
Neuroblastoma is the most common extracranial solid tumor of childhood, with a median age at diagnosis of 17 months
The results reported by Ladenstein et al showed superior five-year event-free survival (EFS) and overall survival (OS) when dinutuximab beta-based immunotherapy with or without IL-2 was included in maintenance therapy, compared with the group treated with isotretinoin alone
These findings were reported in a paper by Ladenstein et al [21], in which authors concluded that dinutuximab beta and isotretinoin without subcutaneous IL2 is to be considered the standard care for high-risk neuroblastoma patients after induction and high-dose chemotherapy (HDT) with stem cell transplantation (SCT)
Summary
Neuroblastoma is the most common extracranial solid tumor of childhood, with a median age at diagnosis of 17 months. The role of IL-2 administered in association with dinutuximab beta is controversial, even though the results of the new randomization in SIOPEN trial, regarding the addition of IL-2 to dinutuximab beta and isotretinoin, showed that IL-2 did not improve outcome, but increased toxicity These findings were reported in a paper by Ladenstein et al [21], in which authors concluded that dinutuximab beta and isotretinoin without subcutaneous IL2 is to be considered the standard care for high-risk neuroblastoma patients after induction and HDT with SCT. Dinutuximab beta is approved in the European Union for the treatment of high-risk neuroblastoma in pediatric patients aged >12 months It can be used both in patients who have achieved at least a partial response to the induction chemotherapy followed by myeloablative therapy and SCT and in patients who have relapsed or refractory neuroblastoma with or without residual disease, after stabilization of any actively progressing disease. We used filters to select articles available in the English language and articles with available full texts
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