Phase I study of intraventricular infusions of autologous ex vivo expanded NK cells in children with recurrent medulloblastoma and ependymoma. Issue 8 (10th March 2020)

• Record Type: Journal Article
• Authors: Khatua, Soumen; Cooper, Laurence J N; Sandberg, David I; Ketonen, Leena; Johnson, Jason M; Rytting, Michael E; Liu, Diane D; Meador, Heather; Trikha, Prashant; Nakkula, Robin J; Behbehani, Gregory K; Ragoonanan, Dristhi; Gupta, Sumit; Kotrotsou, Aikaterini; Idris, Tagwa; Shpall, Elizabeth J; Rezvani, Katy; Colen, Rivka; Zaky, Wafik; Lee, Dean A; Gopalakrishnan, Vidya
• Is Part Of: Neuro-oncology. Volume 22:Issue 8(2020)
• Page Start: 1214
• Page End: 1225
• Publication Date: 2020-03-10
• Subjects: immunotherapy -- intraventricular infusions -- natural killer cells -- recurrent brain tumors; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noaa047
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Background: Recurrent pediatric medulloblastoma and ependymoma have a grim prognosis. We report a first-in-human, phase I study of intraventricular infusions of ex vivo expanded autologous natural killer (NK) cells in these tumors, with correlative studies. Methods: Twelve patients were enrolled, 9 received protocol therapy up to 3 infusions weekly, in escalating doses from 3 × 10 6 to 3 × 10 8 NK cells/m 2 /infusion, for up to 3 cycles. Cerebrospinal fluid (CSF) was obtained for cellular profile, persistence, and phenotypic analysis of NK cells. Radiomic characterization on pretreatment MRI scans was performed in 7 patients, to develop a non-invasive imaging-based signature. Results: Primary objectives of NK cell harvest, expansion, release, and safety of 112 intraventricular infusions of NK cells were achieved in all 9 patients. There were no dose-limiting toxicities. All patients showed progressive disease (PD), except 1 patient showed stable disease for one month at end of study follow-up. Another patient had transient radiographic response of the intraventricular tumor after 5 infusions of NK cell before progressing to PD. At higher dose levels, NK cells increased in the CSF during treatment with repetitive infusions (mean 11.6-fold). Frequent infusions of NK cells resulted in CSF pleocytosis. Radiomic signatures were profiled in 7 patients, evaluating ability to predict upfront radiographic changes, although they did not attain statistical significance. Conclusions: This study demonstrated feasibility of production and safety of intraventricular infusions of autologous NK cells. These findings support further investigation of locoregional NK cell infusions in children with brain malignancies.