Immune checkpoint inhibition for pediatric patients with recurrent/refractory CNS tumors: a single institution experienc
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CLINICAL STUDY
Immune checkpoint inhibition for pediatric patients with recurrent/ refractory CNS tumors: a single institution experience Chantel Cacciotti1 · Jungwhan Choi2 · Sanda Alexandrescu3 · Mary Ann Zimmerman1 · Tabitha M. Cooney1 · Christine Chordas1 · Jessica Clymer1 · Susan Chi1 · Kee Kiat Yeo1 Received: 15 May 2020 / Accepted: 25 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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 nongerminomatous 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. Keywords Immunotherapy · Pediatric · CNS tumors · Recurrence · PD-1 and CTLA4
Introduction
Susan Chi and Kee Kiat Yeo have contributed equally to the supervision of this work. * Kee Kiat Yeo [email protected] 1
Dana Farber/Boston Children’s Cancer and Blood Disorder Center, Boston, MA, USA
2
Department of Radiology, Boston Children’s Hospital, Boston, MA, USA
3
Department of Pathology, Boston Children’s Hospital, Boston, MA, USA
Immune checkpoint inhibitors (ICIs) are a class of immunotherapy drugs that block co-inhibitory signaling pathways and promote T cell mediated immune response against tumor cells [1, 2]. Most commonly, these inh
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