Neurotoxicity of immune checkpoint inhibitor therapy
Research type
Research Study
Full title
Neurotoxicity of immune checkpoint inhibitor therapy: A UK-wide case series
IRAS ID
336869
Contact name
Rachel Norman
Contact email
Sponsor organisation
Cardiff & Vale NHS Trust
Duration of Study in the UK
1 years, 0 months, 1 days
Research summary
Research Summary
Cancer treatment that harnesses the patients’ own immune system to destroy cancer cells (immunotherapy) has had a profound effect on survival rates. However, side-effects (neurotoxicity) are common and potentially life-changing/threatening. Neurotoxicity can affect all parts of the nervous system including inflammation of the brain, spinal cord, peripheral nerves and muscles. The number of affected patients is not clear but has been reported to occur in up to 6% of treated patients.(2)
Currently, there is a limited description of the features of neurotoxicity related to these new treatments and little evidence for how to best manage such cases. Current approaches involve stopping immunotherapy and starting treatment with steroids, which adds additional risks and the potential to affect cancer outcomes. Several research areas therefore urgently need addressing: 1) identification of risk factors that predispose patients to neurotoxicity; 2) understanding the underlying mechanisms of how neurotoxicity occurs; 3) identifying the best treatment strategies; 4) how best to restart immunotherapy after neurotoxicity has occurred; 5) understand the effects of different treatment strategies on cancer outcomes; 6) the economic impact of failed treatment.
As part of an established group of neurologists and oncologists, the aim of this project would be to collect, collate and analyse already existing clinical data across the UK to produce a detailed picture of the clinical presentation and management of patients experiencing neurotoxicity. The outcome would help to inform the identified research questions and lay the foundations for future work.
In particular, the aims of this project are: 1) collect data to produce a detailed picture of the clinical presentation of patients with neurotoxicity; 2) understand how neurotoxicity is managed across the UK; 3) Determine how often neurotoxicity occurs; 4) investigate cancer outcomes in those patients experiencing neurotoxicity; 5) Understand how often patients are retreated with immunotherapy after experiencing neurotoxicity.
Summary of results
Some cancer treatments work by helping the immune system attack cancer cells. These drugs, called immune checkpoint inhibitors (ICIs), can be very effective, but occasionally the immune system can mistakenly attack healthy parts of the body, including the brain, spinal cord, nerves, or muscles. These complications are known as neurological immune-related adverse events (N-irAEs) and can sometimes be serious or even life-threatening.
This study looked at how often neurologists were involved in caring for patients who developed these neurological side effects and whether their involvement affected diagnosis and treatment.
What did the researchers do?
Researchers reviewed the medical records of 109 patients from several hospitals in the UK who developed neurological problems after receiving immune checkpoint inhibitor treatment.
They examined:
1. How often neurologists were involved in patient care.
2. What tests were performed.
3. How patients were diagnosed and treated.
4. Whether outcomes differed depending on neurological involvement.What did they find?
Most patients (about 80%) were seen by a neurologist, although this varied considerably between hospitals.
Patients who were assessed by neurologists were:
1. More likely to have specialist tests such as MRI scans, lumar punctures (spinal fluid tests), and nerve and muscle electrical studies.
2. More likely to receive a specific neurological diagnosis rather than a more general label.
3. More likely to receive advanced treatments when needed, including intravenous immunoglobulin (IVIg) or plasma exchange, which help control harmful immune responses.On average, neurological symptoms developed around seven weeks after starting cancer immunotherapy.
A particularly important finding came from one hospital that routinely involved neurologists early whenever a neurological side effect was suspected. In that centre, doctors changed the original explanation for the patient's symptoms in nearly two-thirds of cases (64%), suggesting that early specialist review can substantially improve diagnostic accuracy.
What does this mean for patients?
The study suggests that involving neurologists early when patients develop neurological symptoms after cancer immunotherapy may help:
1. Identify the correct diagnosis more quickly.
2. Ensure the right investigations are performed.
3. Guide the use of specialised treatments when necessary.
4. Avoid misdiagnosis of neurological symptoms.Although the study could not definitively prove that neurologist involvement improves recovery rates, it showed that specialist assessment often changed clinical decision-making and led to more detailed investigation and management.
Why is this important?
The use of cancer immunotherapy is increasing, meaning that neurological side effects are likely to become more common. The authors conclude that hospitals should develop more consistent approaches for assessing and managing these complications, with early access to neurological expertise.
Key Message
When neurological symptoms occur during cancer immunotherapy, early involvement of a neurologist appears to improve diagnostic accuracy and helps ensure patients receive appropriate investigations and treatments. Standardising this approach across healthcare systems could improve care for patients experiencing these rare but potentially serious side effects.
REC name
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REC reference
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