Improved Outcomes for Older Children, Adolescents, and Young Adults With Neuroblastoma in the Post‐Immunotherapy Era: An Updated Report From the International Neuroblastoma Risk Group

ABSTRACT Background We describe clinical and biologic characteristics of neuroblastoma in older children, adolescents, and young adults (OCAYA); describe survival outcomes in the post‐immunotherapy era; and identify if there is an age cut‐off that best discriminates outcomes. Methods Patients diagnosed with neuroblastoma at ≥547 days between 2003 and 2022 from the International Neuroblastoma Risk Group Data Commons were compared by age subgroups. Recursive partitioning, dividing younger versus older at all monthly cut‐points between 18 months and 15 years, was undertaken using Cox regression models of event‐free survival (EFS), overall survival (OS), and OS post‐relapse (OSPR). Kaplan–Meier curves of clinical/biologic subgroups were compared with log‐rank tests. Results 7,835 patients met inclusion criteria: 18 months to <5 years ( n = 5841), 5 to <10 years ( n = 1488), 10 to <15 years ( n = 357), and ≥15 years ( n = 149) at diagnosis. Younger patients were more likely to have MYCN amplification (18 months to 5 years: 31%; 5–10 years: 15%) than older (10–15 years: 8%; ≥15 years: 7%) ( p < 0.0001), metastatic disease ( p < 0.0001), and high mitosis‐karyorrhexis index (MKI) ( p < 0.0001) and less likely to have diploid tumors ( p < 0.001). Repeatedly dichotomizing the cohort, younger patients had superior EFS and OS ( p < 0.05) for all cut‐offs ≤40 months (hazard ratios: 1.1–1.3). Among high‐risk OCAYA (International Neuroblastoma Staging System [INSS] Stage 4; n = 5005 [64% of cohort]), those diagnosed 2010–2022 had superior EFS/OS versus 2003–2009 in each age group ( p < 0.0001). OSPR remained poor for all OCAYA (5‐year OSPR 14% ± 0.7%). Conclusions For patients ≥547 days old, any age cut‐off ≤40 months discriminated younger (superior EFS/OS) versus older patients; no cut‐off was optimal. OCAYA diagnosed 2010–2022 (post‐immunotherapy era) had superior outcomes versus 2003–2009. Stratification by comprehensive molecular biomarkers will likely best inform novel therapeutic strategies for OCAYA.