In high-risk neuroblastoma, the presence of metastases in bone marrow (BM) or bones after induction therapy is linked to a worse outlook, although anti-GD2 antibodies such as naxitamab can produce responses in these sites. Here we present the outcomes from a phase I/II clinical study. Treatment cycles consisted of GM-CSF and naxitamab, given intravenously (over 30–90 minutes) on days +1, +3, and +5. During the phase I segment, naxitamab doses were increased stepwise; in the phase II expansion, it was given at the recommended phase II dose (RP2D) of 9 mg/kg/cycle (approximately 270 mg/m²/cycle). Following a major response—defined as complete response (CR) or partial response—cycles were repeated monthly for a total of 5 cycles. Of the 32 participants, 24 (75%) achieved CR, including 12 who met international criteria and 12 who showed resolution of MIBG-avid lesions, as evidenced by negative PET scans. BM CR was achieved in 22 of 23 patients with BM metastases. Among 29 individuals with abnormal ¹²³I-MIBG scans, major responses were seen in 14 of 20 with Curie scores (CS) of 10–25 and in 7 of 9 with CS of 1–9. Five of the 9 patients who had received other anti-GD2 antibodies earlier remained event-free survivors. After the protocol, 18 patients received an anti-neuroblastoma vaccine. The five-year progression-free survival and overall survival rates were 38% and 64%, respectively. Baseline CS, previous second-line treatment, and prior anti-GD2 antibody exposure did not have a statistically significant effect on survival. The combination of naxitamab plus GM-CSF represents a promising approach for primary refractory osteomedullary neuroblastoma, even in cases with substantial disease burden.
