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.