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Neurological sequelae of cancer immunotherapies and targeted therapies
Wolfgang Wick1, Anne Hertenstein1, Michael Platten2
1Department of Neurology and Neurooncology Program, National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Units, Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Abstract:
Neurological complications of cancer and of anticancer treatments can be substantially disabling to patients, especially with classic chemotherapies. As a rare but important complication, targeted therapies might also result in similar unwanted effects, partly because inhibition of VEGF is a common downstream effect. Therapeutic antibodies, such as the CD20-depleting antibody rituximab, and underlying haematological malignancies, can induce long-lasting cellular immunosuppression, predisposing patients to opportunistic CNS infections, such as progressive multifocal leukoencephalopathy, where treatment-induced recovery can result in severe reconstitution of immune inflammatory syndromes of the central nervous system. Immune-related neurological adverse events, particularly from immune-activating checkpoint inhibitors, occur as a result of immune activation, resulting in organ-specific autoimmune-like disease. The prevalence of immune-related neurological adverse events might only be about 1%-a low prevalence compared with toxicities in other organs-but it constitutes new patterns of neurological toxic forms, which could result in considerable morbidity and fatal outcomes. Clinicians should be aware of treatment-associated neurotoxicity, and consider discontinuation of the drug with parallel supportive measures to help patients.
Insights
Cancer treatments, including targeted therapies and antibodies, can cause disabling neurological complications. Clinicians must recognize these neurotoxicities and manage them promptly to improve patient outcomes.
Area of Science:
- Oncology
- Neuroscience
- Immunology
Background:
- Cancer therapies, including chemotherapy, targeted agents, and immunotherapy, can lead to significant neurological complications.
- These complications range from opportunistic infections due to immunosuppression (e.g., progressive multifocal leukoencephalopathy) to immune-related adverse events (irAEs) from immune activation.
- Targeted therapies may cause neurotoxicity through mechanisms like VEGF inhibition, while antibody treatments can lead to prolonged immunosuppression.
Purpose of the Study:
- To highlight the spectrum of neurological complications associated with modern cancer treatments.
- To emphasize the importance of recognizing and managing treatment-related neurotoxicity.
- To inform clinicians about the potential for severe neurological adverse events, including irAEs.
Main Methods:
- Review of known neurological complications associated with various cancer treatment modalities.
- Discussion of underlying mechanisms, including immunosuppression and immune activation.
- Analysis of clinical presentation and potential management strategies.
Main Results:
- Cancer treatments can induce diverse neurological adverse events, affecting patients with both solid tumors and hematological malignancies.
- Therapeutic antibodies (e.g., rituximab) and targeted therapies pose risks of neurotoxicity and opportunistic infections.
- Immune checkpoint inhibitors can trigger immune-related neurological adverse events, presenting as autoimmune-like conditions, with a prevalence of approximately 1%.
Conclusions:
- Awareness of treatment-associated neurotoxicity is crucial for oncologists and neurologists.
- Prompt identification and management, including drug discontinuation and supportive care, are essential for mitigating severe neurological morbidity and mortality.
- Understanding the mechanisms of neurotoxicity is key to developing safer and more effective cancer therapies.
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