- •Pembrolizumab induced an anti-AQP4 antibody-positive NMOSD.
- •The results from flow cytometry of the CSF cells revealed increased plasmablasts.
- •Discontinuation of pembrolizumab with immune therapy led to a complete remission.
While immune checkpoint inhibitors (ICIs) have contributed to the development of therapeutic treatments for previously incurable advanced malignancies, they may induce immune-related adverse events (irAEs) in many organs including the CNS . Because immune checkpoint molecules are predominantly expressed on T cells, irAEs are largely not B cell-mediated. Here, we report a patient who was treated with pembrolizumab (a PD-1 monoclonal antibody) for lung adenocarcinoma with brain metastasis, and who developed anti-aquaporin-4 antibody (AQP4-Ab) positive neuromyelitis optica spectrum disorder (NMOSD). We hypothesized that PD-1 immune checkpoint blockage might induce a B cell-mediated immune response in CNS resulting in this complication, which was further supported by the observation of a transient increase in plasmablasts in their CSF.
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- Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial.Lancet Oncol. 2015; 16: 522-530
- PD-1 regulates germinal center b cell survival and the formation and affinity of long-lived plasma cells.Nat. Immunol. 2010; 11: 535-542
- Neuromyelitis optica spectrum disorder as an initial presentation of primary Sjogren's syndrome.Semin. Arthritis. Rheum. 2011; 40: 343-348
- Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance.Nat. Rev. Clin. Oncol. 2019; 16: 563-580
- Neuromyelitis optica spectrum disorder secondary to treatment with anti-PD-1 antibody nivolumab: the first report.BMC Cancer. 2018; 18: 95
- Aquaporin-4 autoantibodies in a paraneoplastic context.Arch. Neurol. 2008; 65: 629-632
- PD-1 controls follicular t helper cell positioning and function.Immunity. 2018; 49 (e4): 264-274
- Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature.Ann. Oncol. 2017; 28: 377-385
- Seronegative antibody-mediated neurology after immune checkpoint inhibitors.Ann. Clin. Transl. Neurol. 2018; 5: 640-645
- Inflammatory cns disease caused by immune checkpoint inhibitors: status and perspectives.Nat. Rev. Neurol. 2017; 13: 755-763
- Neurological, respiratory, musculoskeletal, cardiac and ocular side-effects of anti-PD-1 therapy.Eur. J. Cancer. 2016; 60: 210-225
Published online: October 14, 2019
Accepted: October 13, 2019
Received in revised form: October 4, 2019
Received: July 14, 2019
© 2019 Elsevier B.V. All rights reserved.