# Single-Center Cohort of Pediatric Patients with High-Risk Neuroblastoma Receiving Immunotherapy

## TL;DR

This study examines the safety and effectiveness of immunotherapy in children with high-risk neuroblastoma, showing promising results with minimal side effects.

## Contribution

The study provides real-world evidence of Dinutuximab beta and Nivolumab's safety and efficacy in relapsed/refractory neuroblastoma cases.

## Key findings

- Two patients achieved remission with Dinutuximab beta and Nivolumab therapy.
- Three patients with inoperable tumors showed partial response but later relapsed.
- Dinutuximab beta was well tolerated with only one serious complication.

## Abstract

High-risk neuroblastoma (NB) still has a high mortality rate despite advancements in therapy. The introduction of Dinutuximab beta has yielded further improvements in survival. The latest data prove that combining immune checkpoint inhibitors show an additional contribution to a more successful therapeutic response. Here, we report a retrospective study on a small institutional cohort of high-risk neuroblastoma patients treated with Dinutuximab beta and Nivolumab in relapsed or refractory (r/r) cases (2021–2024). Of twelve patients, five were administered Dinutuximab beta and three were given Nivolumab in combination due to a residual mass still being present at the end of treatment. Two patients achieved remission, one remains in this state, and another relapsed in 4 months after concluding treatment. The other three patients—with an inoperable residual mass—had partial response while undergoing Nivolumab therapy. Apart from one serious complication resolving spontaneously, the use of Dinutuximab beta was well tolerated. Our results underline the safe use of Dinutuximab beta and also prove its good therapeutic response in an r/r setting.

Background: Neuroblastoma (NB) is one of the most common solid tumors in children, still showing a high mortality rate despite recent advances in therapy. A recent breakthrough was the introduction of Dinutuximab beta, yielding further improvements in survival. Dinutuximab beta is an anti-GD2 monoclonal antibody that targets GD2 expressed on the cell surface of neuroblastoma cells. Evidence suggests that Dinutuximab beta combined with Nivolumab may offer an effective synergistic treatment approach. Methods: In our center, immunotherapy was introduced in 2021 as part of maintenance treatment. The aim of this retrospective study was to analyze our data with a focus on the response, side effect profile and tolerability of Dinutuximab beta in HR and relapsed or refractory (r/r) NB. Results: Between 2021 and 2024, we treated 15 patients with neuroblastoma. Twelve patients had high-risk disease, of whom five received Dinutuximab beta as part of maintenance treatment according to protocol HR-NBL 1.8/SIOPEN. Two patients achieved complete remission after immunotherapy. One achieved long-lasting remission, while another relapsed. Three patients with inoperable tumors developed a partial response, but they relapsed and were diagnosed with metastases later. These patients subsequently initiated treatment with Temozolomide + Irinotecan in combination with Dinutuximab beta and also with Nivolumab as a relapse protocol. Therapeutic responses were assessed by the imaging, pathology and flow cytometry analysis of bone marrow. Apart from one complication (hypotension as part of capillary leak syndrome) subsiding spontaneously, no other severe adverse events were observed. Conclusions: Our experiences confirm that immunotherapy, including Dinutuximab beta and Nivolumab, is safe and well tolerated. The standardization of the application of Dinutuximab beta and in combination with novel therapeutic agents in maintenance and refractory/relapsed cases may contribute to improved treatment outcome results.