Immune checkpoint inhibition for pediatric patients with recurrent/refractory CNS tumors: a single institution experience

Introduction Immune checkpoint inhibition through PD-1 and CTLA-4 blockade has shown efficacy in some adult malignancies and generated interest in pediatrics, including central nervous system (CNS) tumors. We describe our experience with immune checkpoint inhibition in recurrent/refractory pediatric CNS tumors. Methods We performed a retrospective chart review of pediatric patients with recurrent or refractory CNS tumors treated with ipilimumab, nivolumab and/or pembrolizumab at Dana-Farber/Boston Children’s Hospital between 2018 and 2019. Results Eleven patients were identified. Diagnoses included diffuse intrinsic pontine glioma (DIPG) (n = 2), high-grade glioma (HGG) (n = 5), ependymoma (n = 1), craniopharyngioma (n = 1), high-grade neuroepithelial tumor (n = 1) and non-germinomatous germ cell tumor (NGGCT) (n = 1). Eight patients had recurrent disease, while three had refractory disease. Nine patients received combination therapy (ipilimumab/nivolumab); two patients received either nivolumab or pembrolizumab. Median time from diagnosis-to-treatment was 8 months (range 0.8–156). All patients received prior radiation therapy (RT), with median time from RT-to-immunotherapy was 3.8 years. One patient received concurrent then adjuvant immunotherapy with RT. Median duration of treatment was 6.1 months (range 1–25). Therapy was discontinued in nine patients: seven due to disease progression and two due to toxicity (colitis; transaminitis). Other pertinent toxicities included Type 1 diabetes mellitus, hypothyroidism and skin toxicity. Based on iRANO criteria, best responses included partial response (n = 3), stable disease (n = 7) and progressive disease (n = 1). Durable response was noted in two patients. Conclusion Immune checkpoint inhibition was relatively well tolerated in a cohort of pediatric patients spanning several CNS tumor diagnoses. Results from prospective clinical trials will be critical to inform clinical decisions.