Neurological adverse effects associated with anti-PD1 antibodies alone or in combination with ipilimumab: a multicenter case series.

Smith JL, Menzies AM, Cohen JV, Mut-Lloret M, Ozgun A, Spain L, Park J, Quach HT, Pallan L, McQuade J, Feng S, Sandhu S, Atkinson V, Tsai K, Long GV, Larkin J, Eroglu Z, Johnson DB, Sullivan R, Herkes GK, Henderson A, Carlino MS. Melanoma Res. 2022 Sep 23. doi: 10.1097/CMR.0000000000000825. Epub ahead of print. PMID: 36164923.


Anti-programmed cell death protein 1 (PD1) antibodies, pembrolizumab and nivolumab, alone or in combination with ipilimumab, have become standard treatment for melanoma and multiple other malignancies. Neurological adverse effects are rare and have not been well characterized to date. Patients who developed neurological adverse effects while being treated with PD1, alone or in combination with ipilimumab, were retrospectively identified from 10 cancer centers. Fifty-eight patients were included, and the median time from treatment initiation to development of neurological adverse effects was 7 weeks (range, 1-86.5 weeks). Thirty-seven (64%) toxicities affected the peripheral nervous system. Fifty (86%) patients were treated with corticosteroids, with 22 (37%) patients requiring further immunomodulation including intravenous immunoglobulin (16), plasmapheresis (7), mycophenolate mofetil (4), cyclophosphamide (1), and rituximab (1). Twenty-seven (46%) had a complete resolution of their neurological symptoms, and two (4%) patients died secondary to complications from their neurological adverse effects. The response rate of the cancer to immunotherapy was 78%, and the median progression free survival was not reached. Neurological adverse effects can occur with PD1 treatment, do not appear to impact treatment response, but may be irreversible or worsen in some patients. Management may require immunomodulation beyond corticosteroids.