Efficacy of anti-GD2 antibody immunotherapy with filgrastim and teceleukin versus standard treatment with sargramostim, aldesleukin and isotretinoin in children with high-risk neuroblastoma.
In a randomized 35-patient trial of children with newly diagnosed high-risk neuroblastoma and non-progressive disease after intensive initial therapy, dinutuximab alternating with G-CSF/teceleukin produced survival estimates interpreted as comparable to the ANBL0032-based GM-CSF/aldesleukin/isotretinoin regimen, without an obvious difference in frequently recorded grade 3/4 toxicities.
Open original publication →What the AI sees
In a randomized 35-patient trial of children with newly diagnosed high-risk neuroblastoma and non-progressive disease after intensive initial therapy, dinutuximab alternating with G-CSF/teceleukin produced survival estimates interpreted as comparable to the ANBL0032-based GM-CSF/aldesleukin/isotretinoin regimen, without an obvious difference in frequently recorded grade 3/4 toxicities.
Research significance
The trial provides preliminary clinical evidence that G-CSF/teceleukin may serve as an alternative cytokine regimen with dinutuximab where GM-CSF, aldesleukin, and isotretinoin are unavailable; equivalence or noninferiority remains an inference requiring confirmation in a larger phase III trial.
Source abstract
BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF), aldesleukin and isotretinoin are unavailable in Japan, necessitating alternative cytokines for dinutuximab immunotherapy. We compared the efficacy of a regimen containing granulocyte colony-stimulating factor (G-CSF)/teceleukin (regimen A) to that with GM-CSF/aldesleukin/isotretinoin (regimen B) in children with newly diagnosed high-risk neuroblastoma. METHODS: After completing initial therapy including high-dose chemotherapy followed by autologous stem cell transplantation and radiotherapy, children with non-progressive disease were randomized to regimen A or B. Regimen B was identical to the immunotherapy regimen tested in ANBL0032 (six cycles of isotretinoin and five concomitant cycles of dinutuximab alternating with GM-CSF and aldesleukin). Regimen A consisted of six cycles of dinutuximab alternating with G-CSF and teceleukin. Event-free survival (EFS) and overall survival (OS) were compared between two regimens. RESULTS: In total, 35 patients (16 receiving regimen A and 19 receiving regimen B) were enrolled. The 2-year EFS was 80.8% for patients receiving regimen A and 62.3% for those receiving regimen B, and their OS rates were 93.8% and 100.0%, respectively. The hazard ratio of regimen A compared to regimen B for EFS was 0.494 (upper limit of one-sided 70% confidence interval: 0.710), suggesting comparable efficacy of the two regimens. Frequently recorded grade 3/4 adverse events were fever, infection, and hematologic toxicity with no obvious difference in incidence between the regimens. CONCLUSIONS: Our results suggest that the efficacy of the alternative regimen containing G-CSF is comparable to that of the ANBL0032 regimen, providing a rationale for further evaluation in a phase III trial.