Neurological complications of immune check point inhibitor therapy: A report of two cases from Canada

INTRODUCTION:

Presentation of 2 challenging cases of severe neurological complications of cancer immunotherapy.

 

LEARNING NEUROLOGY: ONE CASE AT A TIME

Review the pathogenesis of immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICI) cancer therapy.

Discuss current and potential treatment strategies for neurological irAEs.

 

METHODS and RESULTS:

Detail presentation of clinical presentation, neuro-imaging results, investigations including immunological and paraneoplastic workup results and extensive treatment modalities provided.

 

CONCLUSION and DISCUSSION:

IMMUNE-RELATED ADVERSE EVENTS (irAEs) DUE TO IMMUNE CHECKPOINT INHIBITORS (ICI)

ICI has become the forefront for novel therapy for many cancers refractory to traditional radiation therapy and chemotherapy. (@ 2011)

Neurological complications due to ICI treatment has become more prevalent, although very rare (< 1%) and many case series has been reported in the scientific literature: Unintended immune-mediated inflammation of the Nervous system.

CNS: Meningitis, meningo-encephalitis, immune-mediated encephalitis, cerebellar-ataxia syndrome.

PNS: Acute polyradiculopathy (Guillain-Barre Syndrome), Myasthenia Gravis, Inflammatory myositis.

References (1) & (2).

COMMONLY USED ICI IN CANCER IMMUNOTHERAPY

(1) CTLA-4: IPILIMUMAB first approved for metastatic melanoma.

(2) PD-1: PEMBROLIZUMABand NIVOLUMAB FDA approved for renal cell carcinoma,

non-small cell lung cancer (NSCLC), metastatic melanoma, metastatic head and neck cancer.

(3) PDL-1: Atezolizumab, Avelumab and Durvalumab all approved for urothelial carcinoma and second-line therapy for NSCLC.

Reference (3)

 

References:

(1) Haugh AM etal: Expert OpinDrug Saf. 2020 April; 19(4): 479-488.

doi: 10.1080/14740338.2020.1738382.

(2) Azizi S etal: Ochsner Journal 21: 312-315, 2021

(3) DalakasMC: TherAdv Neurol Disord. 2018; 11:1756286418799864

doi: 10.1177/1756286418799864

(4) Youtube: Immune Checkpoint Inhibitors: Neurological Complications.

Dr. Chu graduated from the Faculty of Medicine, University of Toronto in 1978. He subsequently completed his residency training in Internal Medicine and Neurology at University of Toronto obtaining his FRCPC in both specialties. He opened a private Neurological consultative practice in Etobicoke in 1984 with special interests in electromyography and clinical neuromuscular disorders. Other areas of interests include Stroke, Epilepsy, Movement Disorders including Botox injections and Dementia. He is an Assistant Professor of Medicine (Neurology) at the University of Toronto and is an associate staff Neurologist at the Toronto Western Hospital-University Health Network. He is also a consultant Neurologist at the William Osler Health System in Toronto. He was past president of the Chinese Canadian Medical Society of Ontario. In addition, he had published extensively in peer review journals on the Epidemiology of Cerebrovascular Diseases among Chinese Canadians. He was Chairman of the Research Committee, Chinese Canadian Council of the Heart & Stroke Foundation and now the Chinese Canadian Heart and Brain Association (CCHABA). He has been a popular invited visiting Professor giving lectures in Hong Kong, Peoples’ Republic of China, Taiwan and USA. Since 2020, Dr Chu had been leading a team of researchers/clinicians in carrying out population-based research on the epidemiology of COVID-19 and its cardiac and neurological complications among visible minorities in Ontario. His research work is supported by the Ontario Ministry of Health, the Ontario Health Data Platform (OHDP)and the Department of Medicine, University of Toronto and CCHABA.