Managing Adverse Events Associated with Dinutuximab Beta Treatment in Patients with High-Risk Neuroblastoma: Practical Guidance

Abstract

Neuroblastoma is the most common extracranial solid tumour in children, accounting for 15% of all paediatric cancer deaths. High-risk neuroblastoma is a particularly challenging-to-treat form of disease that requires multimodality treatment, consisting of chemotherapy, surgery, high-dose chemotherapy with autologous haematopoietic stem cell rescue, radiotherapy and differentiation therapy. However, despite intense multimodal treatment regimens, the prognosis for this patient population remains poor. In recent years, immunotherapy with anti-disialoganglioside 2 (anti-GD2) antibodies was found to improve survival rates for patients with high-risk neuroblastoma. Based on studies led by the SIOPEN (International Society of Paediatric Oncology European Neuroblastoma) group, the anti-GD2 antibody dinutuximab beta was approved for use in high-risk neuroblastoma by the European Medicines Agency and has been implemented into the standard of care in many countries across Europe. However, immunotherapy with dinutuximab beta is associated with a number of adverse events that may be challenging for clinicians, such as pain, fever, hypersensitivity reactions and capillary leak syndrome. While these adverse events are considered manageable, there are currently no formal guidelines to support clinicians with their management. The aim of this article is to discuss the management of the most common adverse events encountered in clinical practice and to provide practical guidance to assist clinicians in minimising toxicity associated with dinutuximab beta. Key PointsDinutuximab beta can cause adverse events that warrant consideration and management.Most common adverse events include pain, fever, allergy and capillary leak syndrome.Practical guidance is provided on the management of the most common adverse events.

Dinutuximab beta plus conventional chemotherapy for relapsed/refractory high-risk neuroblastoma: A single-center experience

“…Before the introduction of immunotherapy, long-term remission could be achieved in about 40% of HR patients with multimodal treatment including induction chemotherapy, surgery, myeloablative chemotherapy with autologous stem cell rescue, radiation and maintenance therapy with isotretinoin (1-3). Anti-disialoganglioside 2 (anti-GD2)-based immunotherapy has altered the perspective for patients with high-risk NB (4).…”

Immunotherapy with anti‐GD2 monoclonal antibody in infants with high‐risk neuroblastoma

“…Treatment with 3F8 and naxitamab proved safe, feasible, and effective in HR‐NB infants. Acute toxicity was similar with the two mAbs and was indistinguishable from that observed with these 4‐7 and other anti‐G D2 mAbs 12,14,15,32 in older patients. The short infusions and manageable toxicity allowed outpatient treatment.…”

Dinutuximab Beta in Children with High-Risk Neuroblastoma: Experience from a Single Center in Croatia

“…In line with data from the HR-NBL1 SIOPEN study, the tolerability profile of dinutuximab beta generally improved with subsequent cycles [ 8 ], and all AEs were manageable with supportive therapy. Pain, which was one of the most common AEs in patients receiving dinutuximab beta in clinical trials [ 8 , 21 ], was well managed with analgesics as recommended [ 14 ]. Only two patients reported moderate pain in the current case series, one of whom also received IL-2, which has been shown to be associated with a higher incidence of pain when combined with dinutuximab beta [ 8 , 21 ].…”

“…Pain, which was one of the most common AEs in patients receiving dinutuximab beta in clinical trials [ 8 , 21 ], was well managed with analgesics as recommended [ 14 ]. Only two patients reported moderate pain in the current case series, one of whom also received IL-2, which has been shown to be associated with a higher incidence of pain when combined with dinutuximab beta [ 8 , 21 ]. The feasibility, tolerability and effectiveness of dinutuximab beta administration in real-world clinical practice was also demonstrated in a recent single-center experience in Slovakia [ 22 , 23 ].…”