Intravenous immunoglobulin with prednisone and risk-adapted chemotherapy for children with opsoclonus myoclonus ataxia syndrome associated with neuroblastoma (ANBL00P3): a randomised, open-label, phase 3 trial

Intravenous immunoglobulin with prednisone and risk-adapted chemotherapy for children with opsoclonus myoclonus ataxia syndrome associated with neuroblastoma (ANBL00P3): a randomised, open-label, phase 3 trial
This is the first randomized clinical trial in patients with opsoclonus-myoclonus-ataxia syndrome associated with neuroblastoma. Patients affected by OMA have an excellent prognosis for OS, but face a high risk of long-term neuro-cognitive sequelae, including developmental delay, speech and language deficiencies, motor sequelae, ataxia, psychiatric symptoms. The study aims at assessing the response to treatment with prednisone and risk-adapted chemotherapy, and at understanding the role of IVIG.
This was a randomized, phase 3 trial run by the Children's Oncology Group. Children up to 8 years old, with newly diagnosed, biopsy proven neuroblastoma or ganglioneuroblastoma, with OMA were randomized to receive prednisone, risk adapted chemotherapy +/- IVIG. The randomization was stratified by risk assignment.
The severity of OMA and response to treatment was evaluated using the Pike and Mitchell score.
53 patients were enrolled between 2004 and 2013. 62% were female. The response rate was 81% in the IVIG group (21 of 26 patients), and 41% (11 of 27) in the non-IVIG group (odds ratio 6·1, 95% CI 1·5–25·9, p=0·0029). Median follow up for patients with no progression of OMA was 6.1 years. Toxicity was acceptable, with only one death, occurring in a high-risk patient post bone marrow transplant.
The trial was designed before two important pieces of information became available in the field: 1. the efficacy of dexamethasone pulses is comparable to prednisone, but with much more limited toxicity; 2. role of rituximab in the treatment of OMA. Therefore, the results of this trial may be a bit outdated. Nevertheless, the trial answers an important question regarding the role of IVIG. The lack of information on the long term follow up and neuro-cognitive outcomes is also a limitation of the study.
IVIG significantly improve the response rate in patients with OMA and neuroblastoma or ganglioneuroblastoma treated with prednisone and risk-adapted chemotherapy. Their impact on long term neurocognitive outcome, and their role in patients treated with regimens including rituximab remain unknown.