Antitumor Activity and Tolerability of hu14.18-IL2 with GMCSF and Isotretinoin in Recurrent or Refractory Neuroblastoma: A Children’s Oncology Group Phase II Study

Shusterman S, Naranjo A, Van Ryn C, Hank JA, Parisi MT, Shulkin BL, Servaes S, London WB, Shimada H, Gan J, Gillies SD, Maris JM, Park JR, Sondel PM. Antitumor Activity and Tolerability of hu14.18-IL2 with GMCSF and Isotretinoin in Recurrent or Refractory Neuroblastoma: A Children’s Oncology Group Phase II Study. Clin Cancer Res. 2019 Oct 15;25(20):6044-6051. doi: 10.1158/1078-0432.CCR-19-0798. Epub 2019 Jul 29. PMID: 31358541; PMCID: PMC6945765.

Combining anti-GD2 (disialoganglioside) monoclonal antibody with GM-CSF, IL2 and isotretinoin is now FDA-approved for high-risk neuroblastoma (NB) minimal residual disease (MRD) therapy. The humanized anti-GD2 antibody conjugated to IL2 (hu14.18-IL2) has clinical activity in NB and is more effective in NB-bearing mice than antibody and cytokine given separately. We therefore evaluated the safety, tolerability and anti-tumor activity of hu14.18-IL2 given with GM-CSF and isotretinoin in a schedule similar to standard MRD therapy. Hu14.18-IL2 was given at the recommended phase II dose of 12 mg/m2/d on days 4-6 of a 28-day cycle with GM-CSF (250 mg/m2/dose, days 1-2 and 8-14) and isotretinoin (160 mg/m2/day, days 11-25). Tolerability was determined based on the number of unacceptable toxicities observed. Response was evaluated separately for patients with disease measurable by standard radiologic criteria (stratum 1), and for patients with disease evaluable only by I123-metaiodobenzylguanidine (I123-MIBG) scan and/or bone marrow histology (stratum 2).