Discussion
neuroblastoma, SD
DISEASE, NEUROBLASTOMA
This open-label, Phase 2 study evaluated long-term continuous infusion of dinutuximab beta without IL-2 or isotretinoin in patients with relapsed/refractory HR-NB. The best overall response rate (37%), three-year PFS rate (31%), three-year OS rate (66%), and median duration of response (238 days) indicate the clinical activity and efficacy of single-agent dinutuximab beta. Interestingly, the response and survival rates in patients with refractory disease were signifcantly higher than in patients with relapsed disease, suggesting that future trials should be stratified by separating these subgroups.Response and survival are similar to those achieved when dinutuximab beta was administered in combination with IL-2 and isotretinoin in a similar patient population (ORR 41%, three-year PFS rate 33%, three-year OS rate 48%) [Based on this study, single-agent dinutuximab beta administered by long-term infusion is associated with a better safety profile than that reported in a study evaluating dinutuximab beta combined with IL-2 [The pharmacokinetics of dinutuximab beta were similar when administered alone here or co-administered with IL-2 in an earlier study, with mean peak plasma concentration of 11.2 µg/ml (SD 3.2) and 12.56 µg/ml (SD 0.68), respectively [Limitations of the study include the heterogeneity of the enrolled patient population regarding their second-line therapy. The study was conducted to determine the activity of single-agent dinutuximab beta in patients with relapsed/refractory disease who had responded to a second-line therapy that was not predefined in the study protocol. Therefore, as all patients had to be in stable disease to be eligible, the responses must be interpreted with caution. In contrast, many other Phase 2 studies in neuroblastoma included patients with progressive disease at study entry.Despite these limitations, our findings demonstrate that single-agent dinutuximab beta (i.e., without IL-2 and isotretinoin) administered by long-term, continuous infusion in patients with relapsed/refractory HR-NB was associated with improved tolerability and clinically significant and durable response rates that translated into encouraging three-year PFS and OS rates.