Mechanisms, characteristics and treatment of neuropathic pain and peripheral neuropathy associated with dinutuximab in neuroblastoma patients

Stefano Mastrangelo, Serena Rivetti, Silvia Triarico, Alberto Romano, Giorgio Attinà, Palma Maurizi, Antonio Ruggiero

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Article number12648
JournalInternational Journal of Molecular Sciences
Volume22
Issue number23
DOIs
Publication statusPublished - Dec 2021

Keywords

  • Dinutuximab
  • Molecular mechanisms
  • Neuroblastoma
  • Neuropathic pain
  • Pediatric cancer
  • Peripheral neuropathy
  • Treatment

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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