Ipilimumab/Nivolumab-related Opsoclonus-Myoclonus-Ataxia Syndrome Variant in a Patient with Malignant Pleural Mesothelioma

Our plain-English summary of Ipilimumab/Nivolumab-related Opsoclonus-Myoclonus-Ataxia Syndrome Variant in a Patient with Malignant Pleural Mesothelioma, by B. Maller, E. Peguero, T. Tanvetyanon (Journal of Immunotherapy, 2018).

The study

• Authors: B. Maller, E. Peguero, T. Tanvetyanon
• Journal: Journal of Immunotherapy
• Published: 2018;41(9):411-412
• Type of article: Case report
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Ipilimumab and nivolumab are immune-checkpoint inhibitors commonly used for melanoma. The combination is being investigated for its efficacy against several types of cancer, including malignant pleural mesothelioma. Although immune-related adverse events have been reported in patients receiving immune-checkpoint inhibitors, opsoclonus-myoclonus-ataxia syndrome has never been previously described.

Case Presentation: We describe a 74-year-old male with malignant pleural mesothelioma who presented with opsoclonus and marked truncal ataxia ∼10 weeks following immunotherapy with ipilimumab and nivolumab. No myoclonus was present. Oligoclonal bands were detected in cerebrospinal fluid. Treatment with methylprednisolone and intravenous immunoglobulin along with clonazepam and valproic acid resulted in a rapid clinical improvement. A follow-up visit 2 months afterward showed a resolution of opsoclonus and he was able to walk with cane.

Conclusions: A variant of opsoclonus-myoclonus-ataxia syndrome may occur following treatment with ipilimumab and nivolumab.

In plain English

This was a case report of one patient: a 74-year-old white man described as asbestos-exposed, with epithelioid malignant pleural mesothelioma. In a clinical trial, the patient received the immune-checkpoint inhibitors ipilimumab and nivolumab. Treatment was stopped after 2 ipilimumab and 5 nivolumab infusions because the tumor did not shrink, and chemotherapy with pemetrexed and carboplatin followed. About 10 weeks after immunotherapy and 2 weeks after chemotherapy, the patient reported dizziness and could not walk because of imbalance. Examination found involuntary eye movements (opsoclonus) and marked truncal ataxia, but no myoclonus. Spinal fluid showed signs of inflammation, including oligoclonal bands, and infection tests were negative. Doctors diagnosed a variant of opsoclonus-myoclonus-ataxia syndrome (OMAS). After steroids and intravenous immunoglobulin, plus clonazepam and valproic acid, the eye movements resolved. At 8 weeks the patient could walk with a cane. The authors concluded that the immunotherapy most likely triggered the OMAS. They said they could not rule out a cancer-triggered (paraneoplastic) form or a role for the chemotherapy.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: case report (single patient)
• Who was studied: One 74-year-old white male, described as asbestos-exposed, with epithelioid malignant pleural mesothelioma (5% PD-L1 expression) who took part in a clinical trial of ipilimumab and nivolumab
• Exposure: The exposure studied was immunotherapy: intravenous ipilimumab 1 mg/kg every 6 weeks and nivolumab 3 mg/kg every 2 weeks, stopped after 2 ipilimumab and 5 nivolumab infusions. Chemotherapy with pemetrexed 500 mg/m2 and carboplatin AUC5 followed. Asbestos exposure is mentioned but not described.
• Main results:
  • Two weeks after chemotherapy and 10 weeks after immunotherapy, the patient reported dizziness and an inability to walk due to imbalance.
  • On examination the patient had involuntary conjugate horizontal eye movements and marked truncal ataxia. Myoclonus was absent and brain MRI was unremarkable.
  • Cerebrospinal fluid showed mononuclear pleocytosis, elevated protein and positive oligoclonal bands. The tested serum antibodies and infection serology were negative, and a diagnosis of OMAS variant was made.
  • After intravenous methylprednisolone 1 gm/d and immunoglobulin 0.4 gm/kg/d for 5 days, the opsoclonus resolved within one week and the ataxia began to improve.
  • At an outpatient visit 8 weeks after immunosuppression, the opsoclonus remained absent, the ataxia had substantially improved, and the patient could walk with a cane.
• The authors' conclusion: The authors concluded that the OMAS was most likely precipitated by the immunotherapy and that OMAS is a rare but serious complication of ipilimumab-nivolumab combination immunotherapy. They reported that immunosuppression with clonazepam and valproic acid resolved the symptoms promptly.
• Limitations the authors state:
  • As a single case report, the authors could not completely exclude a paraneoplastic (cancer-triggered) form of OMAS.
  • The authors could not exclude the possibility that the pemetrexed and carboplatin chemotherapy precipitated the OMAS.

Topics

Medical terms in this study, explained in our Lexicon: Ipilimumab (Yervoy), Nivolumab (Opdivo), Pleural Mesothelioma, checkpoint inhibitors, Immune-Related Adverse Events, Immunotherapy.

Related studies

• Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial — A. Scherpereel, J. Mazieres, et al. (2019)
• Outcome prediction based on [18F]FDG PET/CT in patients with pleural mesothelioma treated with ipilimumab and nivolumab +/- UV1 telomerase vaccine — S. Thunold, E. Hernes, et al. (2025)
• Malignant mesothelioma clinical trial combines immunotherapy drugs — M.S. Chatwal, T. Tanvetyanon (2018)
• Programmed Death 1 Blockade With Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma — J. Quispel-Janssen, V. van der Noort, et al. (2018)
• CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial — D.A. Fennell, E. Kirkpatrick, et al. (2018)
• Nivolumab for malignant peritoneal mesothelioma — T. Tanaka, Y. Miyamoto, et al. (2020)

Browse more research in Journal of Immunotherapy, or return to medical research.