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Neurological sequelae of cancer immunotherapies and targeted therapies

Journal

LANCET ONCOLOGY
Volume 17, Issue 12, Pages E529-E541

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/S1470-2045(16)30571-X

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Funding

  1. Merck Sharp Dohme
  2. Genentech/Roche
  3. Apogenix
  4. Boehringer Ingelheim
  5. Pfizer
  6. Bristol-Myers Squibb
  7. Celldex
  8. Novocure
  9. Medac
  10. Novartis
  11. Genetech/Roche

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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.

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