Abstract

not-yet-known not-yet-known not-yet-known unknown Introduction: Neuroblastoma (NB) is a malignant tumor of the sympathetic nervous system that usually occurs in children below 5 years of age. High-risk Neuroblastoma (HR-NB) has a poor prognosis despite several treatment strategies. Anti-GD2 monoclonal antibodies (dinutuximab) have recently been added to the standard of care due to improved prognosis. We aimed to systematically assess the outcomes of HR-NB patients treated with anti-GD2 monoclonal antibodies and compare them with those on other treatment regimens. Methods: A comprehensive search strategy was used to search PubMed and the Cochrane Library for articles investigating the effect of dinutuximab on the outcomes of patients with HR-NB. Eligibility criteria included: 1) Diagnosis of HR-NB based on INSS and INRG staging, and MYCN status. 2) Dinutuximab or dinutuximab-beta as the primary agent used in intervention group. 3) Mean/median follow-up time greater than 6 months. Three investigators independently reviewed and extracted relevant articles. Any disagreements were addressed through consultation with other authors. Risk of bias assessment of the selected articles were conducted using the Cochrane Risk of Bias Tool for randomized controlled trials (RCTs) and Newcastle-Ottawa scale for observational studies. Review Manager Software was used to obtain and display the meta-analysis estimates in forest plots. Random effects models were used to calculate the mean difference and overall estimated effects for continuous variables. The main outcomes were all-cause mortality and 5-years event-free survival (5-year-EFS), while the secondary endpoints were the incidence of complete remission and adverse events associated with dinutuximab therapy. Results: Five studies, including two RCTs, two secondary analyses of clinical trials, and one retrospective cohort study, comprising 1,393 participants were included in the analysis. 686 of the patients received dinutuximab while the remaining 707 patients were assigned to other therapies as controls. Dinutuximab was associated with lower all-cause mortality as compared to control [Pooled RR, 0.41; 95% CI, 0.22-0.75, P=0.004, I 2=31%]. 5-year-EFS was also greater for patients treated with dinutuximab [MD: 0.12; 95% CI, 0.09-0.16; P<0.001, I 2=98%]. Dinutuximab was associated with a nonsignificant increase in the incidence of complete remission (Pooled RR, 3.63; 95% CI, 0.64-20.53, P=0.15, I2=70%). The common adverse events associated with dinutuximab therapy included fever, fluid retention, hypotension, hypoxia, and diarrhea. Keywords: dinutuximab, anti-GD2 monoclonal antibody, High-risk Neuroblastoma (HR-NB).