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

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.

Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma.

The reprogramming of a patient's immune system through genetic modification of the T cell compartment with chimeric antigen receptors (CARs) has led to durable remissions in chemotherapy-refractory B cell cancers. Targeting of solid cancers by CAR-T cells is dependent on their infiltration and expansion within the tumor microenvironment, and thus far, fewer clinical responses have been reported. Here, we report a phase 1 study (NCT02761915) in which we treated 12 children with relapsed/refractory neuroblastoma with escalating doses of second-generation GD2-directed CAR-T cells and increasing intensity of preparative lymphodepletion. Overall, no patients had objective clinical response at the evaluation point +28 days after CAR-T cell infusion using standard radiological response criteria. However, of the six patients receiving ≥108/meter2 CAR-T cells after fludarabine/cyclophosphamide conditioning, two experienced grade 2 to 3 cytokine release syndrome, and three demonstrated regression of soft tissue and bone marrow disease. This clinical activity was achieved without on-target off-tumor toxicity. Targeting neuroblastoma with GD2 CAR-T cells appears to be a valid and safe strategy but requires further modification to promote CAR-T cell longevity.

What's it like when you find eating difficult: children's and parents' experiences of food intake.

BACKGROUND: Despite significant advances in supportive care, children and families continue to face many challenges managing the consequences of cancer therapies. The purpose of this study was to explore the eating experiences of children, both at home and in hospital. OBJECTIVE: The objective of the study was to explore the perceptions and experiences of children and their families regarding food intake and discover how nutritional issues are managed by children and families. METHODS: A stratified sample was recruited according to stage in treatment journey, risk of developing nutritional problems, and aged 4 to 12 years undergoing chemotherapy at a cancer center in London, was recruited. This qualitative study involved the use of 2 key visual storytelling techniques: (1) photographs and drawings contained in a scrapbook or diary used as interview stimuli and (2) in-depth interviews with parents. RESULTS: Our study revealed a complex interplay between the context of care, added to an individual child's desires and nutritional needs that are constantly changing during therapy. Failures in the hospital system to meet the nutritional needs of children placed extra stress on parents to provide food for their children. CONCLUSIONS: A relaxed and creative approach to tempting and keeping children engaged with food and eating was a focus for parents, which avoided what they described as making a "big deal about it." Poor information meant that children and parents were not always prepared for the adverse effects of therapies. IMPLICATIONS FOR PRACTICE: This study contributes much to the emerging description of practice guidance and informs strategies that can be used by children and parents.