Anti-GD2 antibody-containing immunotherapy postconsolidation therapy for people with high-risk neuroblastoma treated with autologous haematopoietic stem cell transplantation

BACKGROUND: Neuroblastoma is a rare malignant disease that primarily affects children. The tumours mainly develop in the adrenal medullary tissue, and an abdominal mass is the most common presentation. High‐risk disease is characterised by metastasis and other primary tumour characteristics resulting in increased risk for an adverse outcome. The GD2 carbohydrate antigen is expressed on the cell surface of neuroblastoma tumour cells and is thus a promising target for anti‐GD2 antibody‐containing immunotherapy. OBJECTIVES: To assess the efficacy of anti‐GD2 antibody‐containing postconsolidation immunotherapy after high‐dose chemotherapy (HDCT) and autologous haematopoietic stem cell transplantation (HSCT) compared to standard therapy after HDCT and autologous HSCT in people with high‐risk neuroblastoma. Our primary outcomes were overall survival and treatment‐related mortality. Our secondary outcomes were progression‐free survival, event‐free survival, early toxicity, late non‐haematological toxicity, and health‐related quality of life. SEARCH METHODS: We searched the electronic databases CENTRAL (2018, Issue 9), MEDLINE (PubMed), and Embase (Ovid) on 20 September 2018. We searched trial registries and conference proceedings on 28 October 2018. Further searches included reference lists of recent reviews and relevant articles as well as contacting experts in the field. There were no limits on publication year or language. SELECTION CRITERIA: Randomised controlled trials evaluating anti‐GD2 antibody‐containing immunotherapy after HDCT and autologous HSCT in people with high‐risk neuroblastoma. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, abstracted data on study and participant characteristics, and assessed risk of bias and GRADE. Any differences were resolved by discussion, with third‐party arbitration unnecessary. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. We used the five GRADE considerations, that is study limitations, consistency of effect, imprecision, indirectness, and publication bias, to judge the quality of the evidence. MAIN RESULTS: We identified one randomised controlled trial that included 226 people with high‐risk neuroblastoma who were pre‐treated with autologous HSCT. The study randomised 113 participants to receive immunotherapy including isotretinoin, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), interleukin‐2, and ch14.18, a type of anti‐GD2 antibody also known as dinutuximab. The study randomised another 113 participants to receive standard therapy including isotretinoin. The results on overall survival favoured the dinutuximab‐containing immunotherapy group (hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31 to 0.80; P = 0.004). The results on event‐free survival also favoured the dinutuximab‐containing immunotherapy group (HR 0.61, 95% CI 0.41 to 0.92; P = 0.020). Randomised data on adverse events were not reported separately. The study did not report progression‐free survival, late non‐haematological toxicity, and health‐related quality of life as separate endpoints. We graded the quality of the evidence as moderate. AUTHORS' CONCLUSIONS: The evidence base favours dinutuximab‐containing immunotherapy compared to standard therapy concerning overall survival and event‐free survival in people with high‐risk neuroblastoma pre‐treated with autologous HSCT. Randomised data on adverse events are lacking, therefore more research is needed before definitive conclusions can be made regarding this outcome.