Strategies to manage the adverse effects of immunotherapy with dinutuximab beta in neuroblastoma: an Italian experience and literature review

Purpose: Patients with high-risk neuroblastoma (HR NB) frequently present with metastases in the bone marrow and bone. Approximately 15% of these patients are refractory to induction therapy, and 50% relapse. Dinutuximab beta is an anti-GD2 monoclonal antibody approved in Europe for maintenance therapy of pediatric patients with HR NB. Immunotherapy with anti-GD2 antibodies improves the survival of children with HR NB and relapsed or refractory disease. It is associated with adverse events, such as pain, fever, allergic reactions, capillary leak syndrome, and diarrhea. This manuscript aims to propose a practical guide in support and prevention treatment of adverse events. Methods: MEDLINE was searched using the terms "GD2," "ch14.18/CHO," "anti-GD2 antibody," "dinutuximab beta," and "neuroblastoma." The experts reappraised available evidence discussing different clinical Italian experiences. Results: Neuropathic pain is the main toxicity associated with dinutuximab beta and can be prevented with analgesics, including intravenous opioids and gabapentin by mouth. The intensity of the supportive treatment decreases from course to course. Conclusion: In the experience of the authors, adverse events associated with dinutuximab beta may be prevented and managed in experienced centers. The supportive therapy may be reduced after the first cycle to improve the quality of life.