Extended cycles of anti‑GD2 antibody dinutuximab beta treatment combined with chemotherapy in patients with relapsed or refractory neuroblastoma: A retrospective study

Relapsed or refractory high-risk neuroblastoma (R/R HR-NB) is associated with a poor prognosis. Although 5 cycles of anti-GD2 immunotherapy with dinutuximab beta show efficacy, the regimen needs optimization. The present study evaluated the use of extended dinutuximab beta immunotherapy combined with chemotherapy in pediatric patients with R/R NB. In this single-center retrospective study, children with a median age 5.1 years (range, 2.0-11.1 years) with R/R HR-NB who were treated with >5 cycles of dinutuximab beta (10 mg/m²/day for 10-days per 35-day cycle), granulocyte-macrophage colony-stimulating factor (GM-CSF) and isotretinoin, plus chemotherapy, were included. The primary outcome of the study was objective response rate (ORR). Secondary outcomes included disease control rate, progression-free survival (PFS), overall survival (OS) and safety. A total of 30 patients (24 refractory and 6 relapsed) received dinutuximab beta immunotherapy for a median of 7 cycles (range, 6-12 cycles). Patients with residual disease showed the best ORR of 65%. ORR and complete response (CR) rates improved from 40 and 20%, respectively, at cycle 5/6, to 55 and 30%, respectively, with extended therapy. Notably, 38.5% of patients achieved the best response during cycles beyond the standard 5 cycles. The CR maintenance rate was 90% of patients without residual disease. The 2-year PFS and OS rate were 83.2 and 94.7%, respectively, with higher outcomes in CR patients (2-year PFS rate, 90.0%; 2-year OS rate, 100.0%). Commonly observed grade ≥3 adverse events during the extended phase included infections (90%), neutropenia (86.7%), leukopenia (63.3%) and pain (53.3%), and were generally manageable. No immune-related deaths occurred. Overall, cycles beyond the standard 5 cycles of dinutuximab beta with chemoimmunotherapy were effective and tolerable in pediatric patients with R/R HR-NB, demonstrating improved response and survival outcomes.