TY - JOUR
T1 - Neurological adverse effects associated with anti-PD1 antibodies alone or in combination with ipilimumab
T2 - A multicenter case series
AU - Smith, Jessica Louise
AU - Menzies, Alexander M.
AU - Cohen, Justine V.
AU - Mut-Lloret, Margarida
AU - Ozgun, Alpaslan
AU - Spain, Lavinia
AU - Park, John
AU - Quach, Henry T.
AU - Pallan, Lalit
AU - McQuade, Jennifer
AU - Feng, Sophie
AU - Sandhu, Shahneen
AU - Atkinson, Victoria
AU - Tsai, Katy
AU - Long, Georgina V.
AU - Larkin, James
AU - Eroglu, Zeynep
AU - Johnson, Douglas B.
AU - Sullivan, Ryan
AU - Herkes, Geoffrey K.
AU - Henderson, Andrew
AU - Carlino, Matteo S.
N1 - Funding Information:
G.V.L. is supported by the University of Sydney Medical Foundation and an Australian NHMRC Fellowship. A.M.M. is supported by a Cancer Institute NSW Fellowship. No project specific funding was used to undertake this project.
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - 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.
AB - 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.
KW - anti-PD1
KW - immunotherapy
KW - ipilimumab
KW - neurological toxicity
KW - nivolumab
KW - pembrolizumab
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U2 - 10.1097/CMR.0000000000000825
DO - 10.1097/CMR.0000000000000825
M3 - Article
C2 - 36164923
AN - SCOPUS:85141004850
SN - 0960-8931
VL - 32
SP - 451
EP - 459
JO - Melanoma research
JF - Melanoma research
IS - 6
ER -