A safety and feasibility trial of I-131-MIBG in newly diagnosed high-risk neuroblastoma: A Children's Oncology Group study

Introduction I-131-meta-iodobenzylguanidine (I-131-MIBG) is effective in relapsed neuroblastoma. The Children's Oncology Group (COG) conducted a pilot study (NCT01175356) to assess tolerability and feasibility of induction chemotherapy followed by (131)I(-)MIBG therapy and myeloablative busulfan/melphalan (Bu/Mel) in patients with newly diagnosed high-risk neuroblastoma. Methods Patients with MIBG-avid high-risk neuroblastoma were eligible. After the first two patients to receive protocol therapy developed severe sinusoidal obstruction syndrome (SOS), the trial was re-designed to include an I-131-MIBG dose escalation (12, 15, and 18 mCi/kg), with a required 10-week gap before Bu/Mel administration. Patients who completed induction chemotherapy were evaluable for assessment of I-131-MIBG feasibility; those who completed I-131-MIBG therapy were evaluable for assessment of I-131-MIBG + Bu/Mel feasibility. Results Fifty-nine of 68 patients (86.8%) who completed induction chemotherapy received I-131-MIBG. Thirty-seven of 45 patients (82.2%) evaluable for I-131-MIBG + Bu/Mel received this combination. Among those who received I-131-MIBG after revision of the study design, one patient per dose level developed severe SOS. Rates of moderate to severe SOS at 12, 15, and 18 mCi/kg were 33.3%, 23.5%, and 25.0%, respectively. There was one toxic death. The I-131-MIBG and I-131-MIBG+Bu/Mel feasibility rates at the 15 mCi/kg dose level designated for further study were 96.7% (95% CI: 83.3%-99.4%) and 81.0% (95% CI: 60.0%-92.3%). Conclusion This pilot trial demonstrated feasibility and tolerability of administering I-131-MIBG followed by myeloablative therapy with Bu/Mel to newly diagnosed children with high-risk neuroblastoma in a cooperative group setting, laying the groundwork for a cooperative randomized trial (NCT03126916) testing the addition of I-131-MIBG during induction therapy.