Neurotoxicity associated with anti-PD1 therapy: A multi-center case series.

e21641 Background: The anti-PD1 antibodies (PD1) pembrolizumab and nivolumab are now FDA-approved in multiple malignancies. With increased use, rarer immune-related adverse events (irAEs) not well characterized in clinical trials are being identified, including neurotoxicities. Methods: Patients (Pts) who developed neurotoxicites while being treated with PD1 (alone or in combination) were retrospectively identified from 10 cancer centers. Data regarding treatment, toxicity and outcome were examined. Results: 40 pts (38 melanoma and 2 non-small cell lung cancer pts) developed neurotoxicity; 14 on anti-PD1 monotherapy, 23 in combination or sequence with ipilimumab, and 3 on blinded trials or in combination with interferon. The overall response rate was 90% and median progression free survival was not reached. The median time from treatment initiation to development of neurotoxicity was 7 weeks (range 1-86.5 weeks). 8 pts had died, 5 from disease progression and, 2 from neurotoxicity. 26 pts (65%) developed other irAEs. 27 (67.5%) pts developed toxicities affecting the peripheral nervous system including motor sensory neuropathies (6), sensory neuropathies (4), and Myasthenia Gravis (3). 13 (32.5%) pts developed central nervous system toxicities including aseptic meningitis (6) and encephalitis (4). 24 (60%) pts were treated with steroids alone. 9 pts required further immunomodulation including IVIG (7), plasmapheresis (3), MMF (1) and rituximab (1). 17 (43%) had complete resolution of symptoms, 5 (13%) had stable or worsening neurological disease, and 22 ( 55%) were improving at the time of datacut . 10 pts were retreated with PD1, of which 2 developed exacerbation of prior neurological symptoms. Conclusions: While rare, a variety of neurotoxicities can occur with PD1 treatment. Management may require immunomodulation beyond corticosteroids. Given the high response rate observed in this cohort, such toxicities and their management do not appear to negatively impact treatment response.