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

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Abstract

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.

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  1. Susan Chi and Kee Kiat Yeo have contributed equally to the supervision of this work.

Authors and Affiliations

  1. Dana Farber/Boston Children’s Cancer and Blood Disorder Center, Boston, MA, USA

    Chantel Cacciotti, Mary Ann Zimmerman, Tabitha M. Cooney, Christine Chordas, Jessica Clymer, Susan Chi & Kee Kiat Yeo

  2. Department of Radiology, Boston Children’s Hospital, Boston, MA, USA

    Jungwhan Choi

  3. Department of Pathology, Boston Children’s Hospital, Boston, MA, USA

    Sanda Alexandrescu

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  1. Chantel Cacciotti
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Cacciotti, C., Choi, J., Alexandrescu, S. et al. Immune checkpoint inhibition for pediatric patients with recurrent/refractory CNS tumors: a single institution experience. J Neurooncol 149, 113–122 (2020). https://doi.org/10.1007/s11060-020-03578-6

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