Background: Immunotherapy with the anti-GD2 antibody dinutuximab plus sargramostim (GM-CSF), aldesleukin (IL-2) and isotretinoin following consolidation therapy improved outcome for high-risk neuroblastoma (HRNBL) pts enrolled on COG ANBL0032. Randomization was halted in 2009; subsequent pts were non-randomly assigned to immunotherapy. Toxicities and survival were evaluated. Methods: HRNBL pts < 31 years old with a pre-autologous stem cell transplant (ASCT) response of ≥ partial response (PR) were eligible. Demographics, INSS stage, tumor biology, 1993 INRC pre-ASCT response and toxicities were summarized using descriptive statistics. Five-year (yr) EFS and OS from time of study enrollment were estimated. Results: From 2009-2015, 1,183 pts were non-randomly assigned to immunotherapy. 96.7% (n = 1,144) were ≥18 months old and 83.1% (n = 765/921) had stage 4 disease. 45.1% (n = 363/805) of tumors with known biology were MYCN amplified, 94.5% (n = 749/793) had unfavorable histology, and 54.9% (n = 397/723) were diploid. Pre-ASCT, 352 (29.8%) pts had complete response (CR), 418 (35.3%) had very good partial response (VGPR), and 413 (34.9%) had PR. 1,042 (88.1%) pts underwent a single and 141 (11.9%) underwent tandem ASCT. For the entire cohort, 5-yr EFS was 61.1±1.9% and 5-yr OS was 71.9±1.7%. 5-yr EFS and OS for pts ≥18 months of age with stage 4 disease (n = 746) were 58.4±2.3% and 71.0±2.1%. 5-yr EFS and OS were 82.3±4.8% and 86.7±4.2% among pts with stage 3 disease (n = 110). EFS but not OS was superior for those with a CR/VGPR pre-ASCT vs. PR (5-yr EFS: 64.2±2.2% vs. 55.4±3.2%, p = 0.0133; OS: 72.7±2.1% vs. 70.5±2.9%, p = 0.3811). There was a trend toward improved OS for those treated with tandem vs. single transplant (5-yr EFS: 65.9±4.3% vs. 60.4±2.1%, p = 0.1282; OS: 76.5±3.8% vs. 71.2±1.9%, p = 0.0704). Grade ≥3 toxicities ( > 10% of pts) during GM-CSF and IL-2-containing cycles, respectively, included pain (15.6/11.4%), fever (15.1/32.7%), anemia (18.9/21.7%), thrombocytopenia (13.9/17.4%), lymphopenia (12.3/16.0%), and hypokalemia (13.3/25.2%). Additional Grade ≥3 toxicities ( > 10% of pts) included hypoxia (10.1%) during GM-CSF-containing cycles, and anaphylaxis (12.0%), neutropenia (16.1%), hyponatremia (16.5%), and hypotension (13.8%) during IL-2-containing cycles. Conclusions: In this large cohort of HRNBL pts treated with immunotherapy, 5-yr EFS was 61.1%. Superior EFS was observed for pts with stage 3 disease and for those with CR/VGPR pre-ASCT. IL-2-containing cycles were associated with increased toxicity. Clinical trial information: NCT00026312

U.S. National Institutes of Health