Vol.:(0123456789) 1 3 Journal of Neuro-Oncology (2020) 148:291–297 https://doi.org/10.1007/s11060-020-03514-8 CLINICAL STUDY Neurological adverse efects due to programmed death 1 (PD‑1) inhibitors Siyu Shi 1  · Joseph Abi Jaoube 1  · Ruhi Kanwar 1  · Michael C. Jin 1  · Alvaro Amorin 1  · Vamsi Varanasi 1  · Ella Eisinger 1  · Reena Thomas 1  · Justin M. Moore 2 Received: 20 February 2020 / Accepted: 18 April 2020 / Published online: 29 April 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract Purpose PD-1 Immunotherapy is integral in treating multiple cancers, but has been associated with neurological adverse events (nAEs). Our study was aimed at identifying the clinical spectrum of nAEs associated with pembrolizumab and nivolumab. Methods We performed an IRB approved single-center retrospective cohort study on patients receiving either pembroli- zumab or nivolumab. Patients that developed nAEs within 12 months of treatment were identifed. Descriptive statistics were conducted, and diferences between groups were analyzed by the Chi-square or t test method. Results In total, 649 patients were identifed. Seventeen patients (2.6%) developed nAEs. Eight of those were on pembroli- zumab and nine were on nivolumab. Average age was 62.1 years. Ten were males and 7 were females. Most patients had melanoma (6, 35.3%). Patients who developed nAEs more frequently had intracranial lesions at initiation of anti PD-1 therapy compared to those who did not develop nAEs (76.5% vs 27.8%; p-value < 0.001). Fifteen patients (88.2%) permanently stopped PD-1 therapy. In 8 patients, treatment termination resolved symptoms attributed to immune checkpoint blockade. The majority of patients developed grade 3 or 4 nAEs (10 patients, 58.8%), and required hospitalization (11 patients, 64.7%). Eight patients died for nAEs referable causes. Conclusion Pembrolizumab and nivolumab are associated with the development of nAEs associated with increased risk of permanent discontinuation of treatment, hospitalization, and death. Melanoma patients might be at a particularly high risk of such side efects. Future studies are still required to better assess which patients beneft most from such therapies, while minimizing the risk of complications. Keywords Pembrolizumab · Nivolumab · PD-1inhibitors · PD-L1 inhibitors · Neurological adverse events Importance of the study Pembrolizumab and nivolumab are often used in cancer treatment. We report the largest retrospective cohort study analyzing the neurological adverse events (nAEs) of those PD-1 inhibitors. Such therapies carry a risk of developing nAEs that may lead to hospitalization and death. Melanoma patients may be at a higher risk. The presence of intracranial lesions at start of therapy may be associated with an elevated risk of nAEs. The landscape of nAEs associated with PD-1 inhibitors is broad, with encephalitis being the most com- mon in our study. Introduction Immunotherapy is an increasingly integral component of cancer treatment. Specifcally, anti programmed death 1 (PD-1) monoclonal antibodies target T-cells to help enhance the anti-neoplastic immune response. Physiologically, the interaction between PD-1 receptors and their ligands is This work was accepted and presented as a poster presentation at the American Academy of Neurology 2019 Annual Meeting. * Justin M. Moore jmoore4@bidmc.harvard.edu 1 Department of Oncology, Stanford School of Medicine, Stanford, CA, USA 2 Neurosurgery Service, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Boston, MA 02215, USA