Highlights
- •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.
Abstract
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 [1]. 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.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Multiple Sclerosis and Related DisordersAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- 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
Article info
Publication history
Published online: October 14, 2019
Accepted:
October 13,
2019
Received in revised form:
October 4,
2019
Received:
July 14,
2019
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
