Neurological sequelae of cancer immunotherapies and targeted therapies

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.