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

Abstract

Introduction 131I‐meta‐iodobenzylguanidine (131I‐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 131I−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 131I‐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 131I‐MIBG feasibility; those who completed 131I‐MIBG therapy were evaluable for assessment of 131I‐MIBG + Bu/Mel feasibility. Results Fifty‐nine of 68 patients (86.8%) who completed induction chemotherapy received 131I‐MIBG. Thirty‐seven of 45 patients (82.2%) evaluable for 131I‐MIBG + Bu/Mel received this combination. Among those who received 131I‐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 131I‐MIBG and 131I‐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 131I‐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 131I‐MIBG during induction therapy.

A Phase II Trial of a Personalized, Dose-Intense Administration Schedule of 177Lutetium-DOTATATE in Children With Primary Refractory or Relapsed High-Risk Neuroblastoma–LuDO-N

“…In addition, 131 I-mIBG has been randomized as first line treatment, in two of the treatment arms of the currently ongoing Children's Oncology Group (COG) ANBL 1531 Trial ( ClinicalTrials.gov Identifier: NCT03126916), in an effort to target the metastatic disease in an early stage of the treatment. The ANBL 1531 trial uses a weight-based dosing of 131 I-mIBG ( 47 ).…”

MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment

“…While its function in supporting primary tumor removal is well established [ 98 , 99 ], its role in metastasis management after induction chemotherapy is still uncertain [ 100 , 101 ]. Many advancements were achieved to upgrade this technology, increasing performance both in dose shaping and specificity [ 102 ], for example, with the administration of proton therapy [ 100 , 103 ], or 131 I-MIBG [ 104 , 105 , 106 ] instead of standard photon RT. Considering the improvement in HR-NB treatment and the increase in patient survival, more attention is paid to radiotherapy’s toxic effect.…”

Risk Factors for Transplant-Associated Thrombotic Microangiopathy after Autologous Hematopoietic Cell Transplant in High-Risk Neuroblastoma

“…From 2007 to 2011 patients were treated on study or following ANBL0532 (NCT00567567) [10]. From 2012 to 2017 patients were treated on study ANBL09P1 (NCT01175356) or following ANBL12P1 (NCT01798004) or ANBL0532 [32,33].…”