IMMU-14. MULTI-INSTITUTION ANALYSIS OF TREATMENT MATCHING STATUS AND OUTCOMES IN PEDIATRIC CNS TUMOR PATIENTS

Abstract

Abstract BACKGROUND With the advent of immunotherapies and targeted therapies, research is needed to assess how pediatric brain tumor genomic biomarkers may impact treatment modality choice and outcomes. METHODS We conducted a retrospective analysis of 160 pediatric patients (78 male, 82 female) with a median age of 9 years (2 months-26 years) diagnosed with a primary CNS tumor at four academic institutions from 2008-2023. Tumor mutational burden (TMB), treatment type, outcomes, and matching status were analyzed. Matching status refers to the presence of tumor genomic markers that matched with the pharmacologic target. RESULTS Low-grade glioma (N=68, 42.5%) and high-grade glioma (N=36, 22.5%) were the most common tumors. Other tumors included medulloblastoma (N=17, 10.6%), atypical teratoid rhabdoid tumor (N=4, 2.5%), ependymoma (N=8, 5%), ganglioglioma (N=7, 4.4%), other embryonal tumors (N=5, 3.1%), and choroid plexus tumors (N=5, 3.1%). Of the patients who received targeted or immunotherapy (N=30), most patients had matched (N=19) versus unmatched therapy (N=11) and similar survival rates (p=0.44). Although not statistically significant (p=0.065), patients who received standard therapy had higher overall survival rates (N=103/130) compared to those receiving targeted or immunotherapy (N=19/30). When comparing only patients with high TMB tumors (≥3 mutations/megabase), patients were significantly more likely to survive when receiving standard therapy only (N=20/33) versus targeted or immunotherapy (N=1/7) (p=0.026). Notably, targeted and immunotherapy were not used upfront in these cases. Among patients who had progressed or recurrent disease specifically, there was a non-statistically significant trend towards better survival rates for those who received targeted or immunotherapy (p=0.46). CONCLUSIONS Patients with high TMB tumors who received targeted or immunotherapy have worse outcomes than patients with low TMB, or with high TMB receiving standard therapy. High TMB tumors often require therapy for relapsed/refractory disease. These findings are critical for identifying patient subsets in need of alternative treatment options.